reconsidering depression as a risk factor for substance use disorder insights from rodent models

Accepted Manuscript Title: Reconsidering depression as a risk factor for substance use disorder: Insights from rodent models Authors: Virginie Rappeneau, Anne B´erod PII: DOI: Reference: S0149-7634(16)30699-6 http://dx.doi.org/doi:10.1016/j.neubiorev.2017.04.001 NBR 2811 To appear in: Received date: Revised date: Accepted date: 7-11-2016 25-2-2017 1-4-2017 Please cite this article as: Rappeneau, Virginie, B´erod, Anne, Reconsidering depression as a risk factor for substance use disorder: Insights from rodent models.Neuroscience and Biobehavioral Reviews http://dx.doi.org/10.1016/j.neubiorev.2017.04.001 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain Reconsidering depression as a risk factor for substance use disorder: insights from rodent models Virginie Rappeneau1, Anne Bérod1,* INSERM, U1028, CNRS, UMR5292, Lyon Neuroscience Research Centre, Sleep Team, University Lyon 1, University of Lyon, Lyon, France * Corresponding author: Anne Bérod, Ph.D Lyon Neuroscience Research Center CNRS UMR5292-INSERM U1028 Université Claude Bernard Lyon Lyon, France Tel.: (33) 78 77 86 30 FAX: (33) 78 77 10 22 anne.berod@univ-lyon1.fr Highlights      Depression and substance use disorder (SUD) are highly comorbid The biological mechanisms contributing to their strong association remain largely unknown Depression is considered as a risk factor for drug use in clinical practice Critical analysis of studies in rodents does not support depression as a risk factor for drug use Emphasis on newly refined rodent models that mimic hallmarks of depression and SUD is recommended Abstract: 156 words Manuscript body: 7299 N° of Figures: N° of Tables: Abstract Depression and substance use disorder (SUD) often co-exist and are typically associated with an inaccurate diagnosis, worsened clinical course and poor medication adherence compared to either disorder alone To date, the biological mechanisms contributing to their strong association remain largely unknown In this review, we critically analyze preclinical literature on psychostimulant drugs and reconsider the common view that depression is a risk factor for drug use and the development of SUD Unexpectedly, this investigation led us to conclude that depressive-like states in rodents are associated with a low predisposition to drug intake, at least when considering initial, voluntary and regulated psychostimulant intake We identified several conceptual gaps and methodological challenges potentially misleading when modeling depression and SUD comorbidity On the basis of these observations, we propose new innovative perspectives to guide future experiments and advance our knowledge in this field, including the use of newly refined rodent models that better capture hallmarks of depression and SUD Abbreviations: Ø: no difference; ↓: reduction; ↑: increase CPP: Conditioned Place Preference; FR: fixed ratio; inf.: infusion; i.p.: intraperitoneal injection; L-E: Long-Evans; L-H: Lister-Hooded; METH: methamphetamine; PR: progressive ratio; SA: self-administration; S-D: Sprague-Dawley; SDS: Social Defeat Stress; UCMS: Unpredictable Chronic Mild Stress Keywords : Depression; Substance Use Disorder; Psychostimulant; Comorbidity; Vulnerability; Rodent models; Behavior Contents Introduction Depression and substance use disorder comorbidity: why does it occur and matter? Scope of the review: reevaluating depression as a risk factor for psychostimulant intake in rodents Assessing substance use disorder in rodent models of depression: challenges and opportunities 4.1 4.2 Stress conditions as a basis for modeling depression 4.1.1 Unpredictable chronic mild stress 4.1.2 Social defeat stress 4.1.3 Early life stress 4.1.4 Post-weaning social isolation rearing Selective breeding as a basis for modeling depression 4.2.1 Wistar-Kyoto rats 4.2.2 Flinders Sensitive rats 4.2.3 Swim-Low rats 4.2.4 H/Rouen mice General conclusion What further studies are required to advance our understanding in this field? Concluding remarks C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Introduction Co-occurrence of two or more psychiatric diagnoses in the same individual is common in psychiatry (Degenhardt et al., 2003) This form of comorbidity encompasses a wide range of mental health disorders including schizophrenia, mood and anxiety disorders as well as substance use disorder (SUD) Major depressive disorder (hereafter referred to as depression) is one of the most common psychiatric disorders worldwide despite estimates of its lifetime prevalence varying substantially across countries (Kessler and Bromet, 2013) Depression is characterized by a long-lasting and recurrent depressed mood and/or anhedonia referring to a diminished interest or pleasure in most activities (Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) (American Psychiatric Association, 2013) These core symptoms are accompanied by additional symptoms including sleep disturbances, feelings of worthlessness or suicidal ideation Depression is also accompanied by multiple comorbidities, among which substance use and SUD are particularly common SUD is characterized by patterns of escalated and sustained drug intake, loss of control over drug intake, and drug craving ( DSM-5, American Psychiatric Association, 2013) SUD occurs only in individuals whose drug use opportunities develop into a maladaptive pattern of drug taking and seeking (Lopez-Quintero et al., 2011; Wagner and Anthony, 2002) Large scale epidemiological studies document strong associations between drug use, SUD and mental health disorders For instance, prevalence rates of SUD are almost twice as high among individuals with severe depression compared to the general population (Conway et al., 2006; Grant et al., 2016; Swendsen et al., 2010; for review Tolliver et Anton, 2015) Concordantly, depression is to times more prevalent among individuals diagnosed with SUD than those without SUD (Lai et al., 2015) This reciprocal comorbidity has been observed for all pharmacological classes of addictive drugs, including nicotine, alcohol, cannabis, opiates and psychostimulants (Conway et al., 2006; Grant et al., 2016; Grant et al., 2004; Régier et al., 1990) Depression and substance use disorder comorbidity: why does it occur and matter? Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Co-occurrence of depression and SUD in patients who present dual diagnoses has long been recognized as an important consideration in clinical practice Comorbid depression and SUD is typically associated with an inaccurate diagnosis, worsened clinical course, greater functional impairment, and lower medication adherence compared to either disorder alone (Abou-Saleh, 2004; Merikangas and Kalaydjian, 2007) In addition, mental health and SUD treatment professionals are confronted with the difficulties of providing effective care to patients whose problems overlap two health care specialties Several hypotheses have been proposed to explain the high prevalence rate of comorbid mental health disorders (Degenhardt et al., 2003) Comorbidity can be explained in causal terms, the presence of one disorder increasing the likelihood of another to occur (Fig 1a) For example, comorbidity may manifest in individuals who use substances and their specific psychotropic effects to cope with emotional distress and reduce dysphoric symptoms associated with depression (Conway, 2004; Kessler, 2004; Khantzian 1985, 1997; Swendsen 2010) (Fig.1a) In this type of case, treating the underlying depression would have certain benefits for treating SUD However, only a small number of double-blind, placebo-controlled trials have been conducted in substance use-dependent patients with depression in order to evaluate the therapeutic impact of antidepressant pharmacotherapy Several clinical trials have demonstrated a beneficial effect of antidepressants on mood symptoms in patients with comorbid SUD but yet failed to establish their effectiveness on substance use outcomes due to inconsistent results (see Lalanne et al., 2016; Nunes and Levin, 2004; Pettinati et al., 2013) Conversely, substance-induced depression can be observed during acute intoxication and withdrawal from drugs in individuals with SUD (Gawin and Kleber, 1986; Markou and Kenny, 2002) In these patients, symptoms of depression typically disappear within a month or less after abstinence, particularly for those in addiction-treatment settings (Brown and Schuckit, 1988; Nunes and Levin, 2004; Nunes et al., 2004) Comorbidity could also be caused by substance use revealing a latent predisposition toward depression in high-risk individuals which facilitates the expression of depression symptoms (American Psychiatric Association, 2013) Both pathways contribute significantly to the rates of comorbidity between depression and SUD (Schuckit, 2006) Finally, shared predisposing factors Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an such as biological, social or environmental factors may increase the likelihood of depression and SUD explaining their association (Kendler et al., 2003) (Fig.1b) For example, exposure to early adverse life events in the form of child abuse and/or neglect is a risk factor for both depression and SUD in adulthood and might account for some comorbidity (Gerra et al., 2009; Kessler, 1997; Nemeroff, 2016) All these scenarios probably contribute, in various degrees, to how and why depression and SUD comorbidities occur, each with different implications for prevention, treatment and future research Scope of the review: reevaluating depression as a risk factor for psychostimulant intake in rodents In humans, efforts to understand whether depression precedes and influences drug use and the development of SUD have been hampered by both the difficulties in establishing the sequence of disorder onset and the complex nature of comorbidity in individuals with co-existing psychiatric disorders such as anxiety disorders (Gorman, 1996; Merikangas et al., 1998) and polysubstance use and abuse (Connor et al., 2014) Animal models, especially rodents, have improved comprehension of the potential risk factors for depression and drug use, and the mutual interactions between these two disorders These studies have been evaluated in recent comprehensive reviews (see Bardo et al., 2013; Filip et al., 2013; Neisewander et al., 2012; Ng et al., 2016; Paterson and Markou, 2007; Renoir et al., 2012) In particular, converging evidence highlights an enhanced vulnerability to drug use in rodents subjected to social and environmental factors that produce depressive-like behaviors (reviewed in Bardo et al., 2013; Neisewander et al., 2012; Ng et al., 2016) However, regarding depression per se as a contributing factor to drug vulnerability, few studies have focused on the complexity of depression and SUD in terms of heterogeneous symptoms, inter-individual variability or diversity of etiological factors Consequently, there is little evidence from rodent models showing depression as a risk factor for drug use and SUD and many questions and controversies remain unaddressed (Bardo et al., 2013; Filip et al., 2013; Neisewander et al., 2012; Ng et al., 2016) We therefore reviewed preclinical literature to highlight any inconsistencies and further interpret the data We applied a focused approach by only analyzing psychostimulant drugs, including amphetamine, Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an cocaine and methamphetamine, in animal models of depression, rather than systematically compiling and comparing literature on drugs of various pharmacological classes We also critically analyzed the advantages and drawbacks associated with rodent models of depression as well as the design of experimental procedures used to study different aspects of SUD This highlighted some important methodological and conceptual issues which potentially mislead the modeling of depression and SUD comorbidity in rodents Accordingly, we propose new challenges and future perspectives to further advance this field Assessing substance use disorder in rodent models of depression: challenges and opportunities Depression is triggered by multiple, partially overlapping risk factors which are used in rodent models of depression and include: behavioral traits, genetics, life experiences and the environment (Kendler et al., 1999, 2001; Klengel and Binder, 2013; Lohoff, 2010) Rodent models of depression adopted by most laboratories have been recapitulated in several excellent reviews (see Belzung and Lemoine, 2011; Berton et al., 2012; Krishnan and Nestler, 2011; Nestler and Hyman, 2010; Neumann et al., 2011; Slattery and Cryan, 2014 for review) Their validity for preclinical research has been justified by the three criteria laid out by Willner (1984); (i) i.e causative factors (construct validity); (ii) symptomology (face validity); (iii) treatment modalities (predictive validity) In this chapter, we examine whether a depressive-like state influences psychostimulant drug-related behaviors in rodents, concentrating our analysis on two of the most commonly used procedures in drug addiction research: the drug intravenous self-administration and conditioned place preference (CPP) paradigms The self-administration paradigm was initially designed to study the initiation and maintenance of voluntary drug taking It was later refined to emulate behaviors resembling those currently considered hallmarks of SUD in the DSM-5, such as high motivation for drug intake, shift from controlled to compulsive drug taking culminating in the loss of control over drug intake, voluntary abstinence and compulsive relapse (Ahmed and Koob, 1998; Belin-Rauscent et al., 2016; Belin et al., 2016; DerocheGamonet et al., 2004; Vanderschuren etal., 2004) The CPP paradigm is based on a form of Pavlovian Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an conditioning in which animals learn to associate the rewarding properties of psychostimulant drugs with contextual information (Bardo and Bevins, 2000; Tzschentke, 2007) This learned drug-context association is known to play a crucial role in drug use and relapse in both laboratory animals and humans (Bardo and Bevins, 2000) 4.1 Stress conditions as a basis for modeling depression In rodents, exposure to repeated stress is one of the most common approaches for producing depressive-relevant behavioral endpoints (see Belzung and Lemoine, 2011; Berton et al., 2012; Krishnan and Nestler, 2011; Nestler and Hyman, 2010; Neumann et al., 2011; Slattery and Cryan, 2014 for review) Several stress-based models of depression have been employed to determine psychostimulant vulnerability They are reviewed here according to the type of environmental factor used 4.1.1 Unpredictable chronic mild stress (UCMS) represents the primary model of depression in rats over several decades (Moreau et al., 1995; Papp et al., 1991; Willner et al., 1987) It involves exposing rodents to repeated and unpredictable physical stressors (e.g water or food deprivation, exposure to cold temperatures, isolation etc.) over long periods of time (1 week to months) (Nestler and Hyman, 2010; Willner, 2005) Towards the end of the stress procedure, animals exhibit anhedonia-like behavior by a decrease in preference for sweet tasting solution Reversal of this UCMS-induced anhedonia-like behavior can occur with chronic pharmacological antidepressant treatments (Strekalova et al., 2006; Willner et al., 1987) as well as deep brain stimulation of the ventromedial prefrontal cortex (vmPFC) (Hamani et al., 2012; Veerakumar et al., 2014), a non-pharmacological intervention reported to produce long-lasting antidepressant effects in treatment-resistant patients (Berlim et al., 2014; Mayberg, 2009) Although the UCMS model has been the subject of considerable controversy related to poor reproducibility in inducing anhedonia-like behavior (Argyropoulos and Nutt, 1997), it has a high degree of construct, face and predictive validity (Willner, 1997, 2005) To date, a number of UCMS variants have been proposed in both rats and mice to emulate several depressive-related behavioral and physiological impairments (see Nollet et al., 2013; Strekalova et al., 2011 for review) Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Recently, two studies performed in rats indicated no effect of UCMS on the acquisition and maintenance of methamphetamine self-administration using a fixed ratio (FR) schedule of reinforcement as well as the motivation to obtain this drug according to a progressive ratio (PR) schedule of reinforcement (Lewis et al., 2016; Taylor et al., 2016) (Table 1) However, use of the CPP paradigm revealed inconsistent data UCMS decreased amphetamine-induced CPP when performed during the last two weeks of the UCMS procedure (Papp et al., 1993; Papp et al., 1991) In contrast, testing rats 24 h after the last stressor showed no effect of UCMS on methamphetamine-induced CPP and enhanced CPP for low doses of cocaine (Haile et al., 2001; Taylor et al., 2016) (Table 1) Several methodological and procedural aspects limit the interpretation of these results Firstly, it is likely that not all animals exposed to UCMS demonstrated a depressive-like behavior In fact, recent studies indicate that a substantial fraction of animals exposed to UCMS (∼30%) showed no reduction in preference for sweet tasting solution and remained resistant to the development of anhedonia-like behavior (Bergstrom et al., 2008; Bergstrom et al., 2007; Henriques-Alves and Queiroz, 2015; Strekalova et al., 2004) Heterogeneity in individual behavioral responses to UCMS and the relatively large proportion of animals that developed resilience to this procedure possibly biased the aforementioned results, therefore hampering any clear conclusions It is possible that two populations of rats, i.e susceptible and resilient to UCMS, may behave differently regarding psychostimulant self-administration and CPP Although not directly addressing this issue, a recent study emphasized the importance of characterizing behaviors relevant to emotional state when assessing methamphetamine self-administration after exposure to UCMS (Taylor et al., 2016) Indeed, rats displaying high locomotor reactivity to novelty following UCMS self-administered more methamphetamine and showed greater motivation to obtain this drug than rats exhibiting low reactivity to novelty In addition, it should be noted that acute and repeated stressors which induced no depressive-like state increased psychostimulant-induced CPP in animals tested shortly after the last stress exposure (Montagud-Romero et al., 2015; Schindler et al., 2012) In the above-mentioned studies, testing of the CPP Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Papp, M., Muscat, R., Willner, P., 1993 Subsensitivity to rewarding and locomotor stimulant effects of a dopamine agonist following chronic mild stress Psychopharmacology (Berl) 110, 152-158 Papp, M., Willner, P., Muscat, R., 1991 An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress Psychopharmacology (Berl) 104, 255-259 Pare, W.P., 1994 Open field, learned helplessness, conditioned defensive burying, and forced-swim tests in WKY rats Physiol Behav 55, 433-439 Paterson, N.E., Markou, A., 2007 Animal models and treatments for addiction and depression comorbidity Neurotox Res 11, 1-32 Pergadia, M.L., Der-Avakian, A., D’Souza, M.S., Madden, P.A.F., Heath, A.C., Shiffman, S., Markou, A., Pizzagalli, D.A., 2014 Association between nicotine withdrawal and reward responsiveness in humans and rats JAMA Psychiatry 71, 1238–1245 Pettinati, H.M., O'Brien, C.P., Dundon, W.D., 2013 Current status of co-occurring mood and substance use disorders: a new therapeutic target Am J Psychiatry 170, 23-30 Phillips, G.D., Howes, S.R., Whitelaw, R.B., Wilkinson, L.S., Robbins, T.W., Everitt, B.J., 1994 Isolation rearing enhances the locomotor response to cocaine and a novel environment, but impairs the intravenous self-administration of cocaine Psychopharmacology (Berl) 115, 407-418 Piazza, P.V., Deminiere, J.M., Le Moal, M., Simon, H., 1989 Factors that predict individual vulnerability to amphetamine self-administration Science 245, 1511-1513 Piazza, P.V., Le Moal, M., 1998 The role of stress in drug self-administration Trends Pharmacol Sci 19, 67-74 Pierce, R.C., Kumaresan, V., 2006 The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? 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77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Figure Caption 48 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Figr-1 Legend Figure Hypotheses concerning the reasons why comorbidity of depression and substance use disorder might occur: (a) There are causal relationships between the two disorders: substances are used to relieve dysphoric moods and/or substance use induces or reveals a latent predisposition towards depression; (b) Common risk factors promote the concurrent development of depression and substance use disorder 49 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Table Psychostimulant self-administration and CPP-related-behaviors in rodents exposed to chronic stress in adulthood Strain Stress Test duration Drug Timeline Dose Effect Ref Unpredictable Chronic Mild Stress (UCMS) ♂ S-D rats 14 days SA METH ♂ L-E rats 10 days SA METH ♂ S-D rats 14 days CPP METH ♂ S-D rats 10 days CPP Cocaine ♂ L-H rats weeks CPP Amphetamine days after UCMS days after UCMS days after UCMS 24 h after UCMS last weeks of UCMS FR1: 0.05 mg/kg/inf PR: 0.05 mg/kg/inf - Ø intake (FR, PR) - Rats with high reactivity to novelty: ↑ intake (FR, PR) [1] FR1: 0.05 mg/kg/inf - Ø intake [2] 0.06 or 0.25 mg/kg i.p (x5) - Ø CPP [1] mg/kg i.p (x8) - ↑ CPP [3] 0.5-1 mg/kg i.p (x3 or 4) - ↓ CPP [4] [5] Conclusion: No clear influence of UCMS on psychostimulant intake and CPP Social defeat stress (SDS) ♀ L-E rats Twice daily for 21 days SA Cocaine 16 days after last SDS FR1: 0.75 mg/kg/inf PR: 0.3 mg/kg/inf 24h binge, FR1: 0.3 mg/kg/inf ♂ L-E rats 36 days SA Cocaine 17 days after last SDS FR1/FR5 and PR: 0.75 mg/kg/inf 24h binge, FR5: 0.3 mg/kg/inf Cocaine 24 h after last SDS 28 days after last SDS ♂ C57Bl/6 mice 10 days CPP mg/kg i.p (x2) - Vulnerable (72%) Ø intake (FR, PR) ↓ intake (binge) - Resilient (28%) Ø intake (FR, PR) ↑ intake (binge) [6] - Ø intake (limited access) - ↓ intake (binge) [7] - Vulnerable (60%) ↑ CPP - Resilient (40%) ↓ CPP [8] - Vulnerable Ø CPP Conclusion: Depressive-like states as a result of SDS reduce psychostimulant binge intake [1] Taylor, S.B et al., Neuropharmacology, 2016 [2] Lewis, C.R et al, Behav Pharmacol, 2016 [3] Haile, C.N et al., Psychopharmacology (Berl), 2001 [4] Papp, M et al., Psychopharmacology (Berl), 1993 [5] Papp, M et al., Psychopharmacology (Berl), 1991 [6] Shimamoto, A et al., Psychopharmacology (Berl), 2015 [7] Miczek, K.A et al., J Neurosci, 2011 [8] Krishnan, V et al, Cell, 2007 50 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Table Psychostimulant self-administration and CPP-related-behaviors in adult rodents exposed to early life stress Strain Stress duration Test Drug Timeline Dose Effect Ref Maternal separation (MS) ♂ S-D rats vs NH MS180 at P2-12 SA Cocaine P46 - ↓ intake (FR, for all doses) FR5, ascending doses: 0.125, - Ø PR 0.25, 0.5 mg/kg/inf - Ø extinction PR: 0.5 mg/kg/inf - ↓ cocaine-induced reinstatement ♂ L-E rats vs NH, MS15 MS180 at P2-15 SA Cocaine  ± P90 FR3, PR : 0.0625 to 1.0 mg/kg/inf ♂/♀ L-H rats vs MS5 MS360 at P5-20 SA Cocaine ♂ L-E rats vs MS15 MS180 at P2-14 SA METH ♂ L-E rats vs MS15 MS180 at P2-14 SA METH ♂ S-D rats vs AFR ♂ S-D rats vs no MS MS180 at P2-14 Handling at P25-30 MS180 at P2-14 Handling at P25-30 - ↑ intake at 0.0625 mg/kg/inf - ↓ intake at 0.05 mg/kg/inf Acquisition FR1: 0.05, 0.08, - ↑ acquisition at  ± P77 0.5 mg/kg/inf 0.08mg/kg/inf (♀) - Ø intake after acquisition - ↑ acquisition ± P60  FR1: 0.05 mg/kg/inf - Ø extinction and cueinduced reinstatement - ↑ SA with no exposure to CVS - Ø SA with exposure to P55 ± CVS FR1: 0.05 mg/kg/inf CVS - Ø extinction, reinstatement [1] [2] [3] [4] [5] [6] CPP METH P37: inj P43: inj P50: inj mg/kg, i.p (x4 or 8) - Ø CPP [7] CPP METH P32 mg/kg, i.p (x4) - ↓ CPP [8] Conclusion: No clear influence of MS on psychostimulant intake and CPP Neonatal Isolation (NI) ♂/♀ S-D rats vs NH NI 1h/day at P2-9 SA Cocaine P70-120 ♂ S-D rats vs NH NI 1h/day at P2-9 SA Cocaine P70-90 ♂/♀ S-D rats vs NH NI 1h/day at P2-12 SA Cocaine P90 - ↑ acquisition, maintenance at lower Acquisition FR1: 0.0625 to doses 0.5 mg/kg/inf - Ø extinction of Maintenance FR1 or PR: 0.5 responding mg/kg/inf - Ø cocaine-induced reinstatement Acquisition FR1: 0.5 mg/kg/inf - ↑ acquisition, Maintenance FR2/FR3 and maintenance at lower PR : 0.125, 0.25, 0.5, 1.0 doses mg/kg/ inf - Ø intake (♂) Acquisition FR1, continuous - ↑ intake (♀) access (FR1, 24-h binge): - ↓ extinction 1.5 mg/kg/inf - ↑ cue-reinstatement 51 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn [9] [10] [11] [12] [13] C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an ♂ L-E rats vs NH15 ♂ C57BL/6 mice vs NH NI 3h/day at P2-8 NI 6h/day at P5-9 CPP METH P60 mg/kg i.p (x4) - ↑ CPP (♂) - Ø CPP (♀) [14] CPP Cocaine P65 mg/kg i.p (x2) - ↓ CPP [15] Conclusion: NI increases the propensity to acquire and maintain psychostimulant intake Abbreviations: Ø: no difference; ↓: reduction; ↑: increase; ±: around AFR: Animal/standard facility rearing; CPP: Conditioned Place Preference; CVS: chronic variable stress; FR: fixed ratio; inf.: infusion; i.p.: intraperitoneal injection; L-E: Long-Evans; L-H: Lister-Hooded; METH: methamphetamine; MS: maternal separation; NH: NonHandled; NI: Neonatal Isolation; P: post-natal day; PR: progressive ratio; SA: self-administration; S-D: SpragueDawley [1] O'Connor, R.M et al., Neuropharmacology, 2015 [2] Moffett, M.C et al., J Pharmacol Exp Ther, 2006 [3] Moffett, M.C et al., Biochem Pharmacol, 2007 [4] Matthews, K et al., Psychopharmacology, 1999 [5] Lewis, C.R et al., Front Psychiatry, 2013 [6] Lewis, C.R et al., Behav Pharmacol, 2016 [7] Faure, J et al., Metab Brain Dis, 2009 [8] Dimatelis, J.J et al., Metab Brain Dis, 2012 [9] Kosten, T.A et al., Brain Res, 2000.[10] Kosten, T.A et al., Behav Brain Res, 2004 [11] Kosten, T.A et al., Neuropsychopharmacology, 2006 [12] Zhang, X.Y et al., Psychopharmacology, 2005 [13] Lynch, W.J et al., Neuropsychopharmacology, 2005 [14] Hensleigh, E., Pritchard, L.M., Behav Brain Res, 2014 [15] Hays, S.L et al., Behav Brain Res, 2012 52 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Table Psychostimulant self-administration and CPP-related-behaviors in adult rodents exposed to post-weaning social isolation rearing compared to group-housed animals Strain Stress duration Test Drug Timeline Dose Effect Ref Post-weaning social isolation rearing (SI) ♂ L-E rats FR1: 0.04 to 0.25 mg/kg/inf - Tendency to ↑ SA [1] FR1: mg/kg/inf Acquisition FR1: 1.5 mg/kg/inf Dose-response: 1.5 to 0.0234 mg/kg/inf FR1: 0.04, 0.08, 0.16, 0.32, 0.64 mg/kg/inf - Ø SA [2] - ↓ Acquisition and shift dose-response curve to the right [3] - ↑ SA at 0.04 mg/kg [4] P61-65 FR1: 0.5 mg/kg/inf - ↑ SA [5] Cocaine P77 FR1: 0.083, 0.25, 1.5 mg/kg/inf - ↑ SA only at low dose (0.083 mg/kg/inf.) [6] SA Cocaine P63 Acquisition: 0.1-1 mg/kg/inf P21-42 weeks of group housing SA Cocaine P84 P21-51 SA Amphetamine ±P53 P21-49 CPP Cocaine P51-55 P21-63 CPP Cocaine P63 P21-63 CPP Amphetamine P63 P21-63 CPP Amphetamine P63 P21-42 CPP Amphetamine P63-70 P21-63 SA Cocaine SA Cocaine from P21 SA Cocaine P140 P21-63 SA Cocaine P54 P22-55 SA Cocaine P21-77 SA P21-63 ♂ L-E rats ♂ L-H rats ♂ L-E rats ♂ S-D rats ♂ L-H rats ♂ L-E rats ♂ L-H rats ♂ S-D rats ♂ S-D rats ♂ L-E rats ♂ L-E rats ♂ L-H rats ♂ S-D rats P63 - ↑ SA at 0.5 and mg/kg/inf - ↑ acquisition, Acquisition FR1: ↑ breakpoint 0.083 mg/kg/inf - Ø cue-, cocaine- or PR: 0.25 mg/kg/inf stress-induced reinstatement Acquisition FR1: 0.03- - Ø SA at 0.03 mg/kg/inf 0.1 mg/kg/inf ↑ SA at 0.1 mg/kg/inf mg/kg i.p (x2) - ↓ CPP 0.31, 0.63, 1.25, or 2.5 - ↓ CPP mg/kg i.p (x4) 0.031, 0.063, 0.125, 0.25 or mg/kg i.p - Ø CPP (x4) 1.5 and mg/kg i.p - ↓ CPP (x4) mg/kg i.p (x1, or 7) - ↑ rate acquisition CPP - ↓ rate of extinction CPP [7] [8] [9] [10] [11] [11] [12] [13] Conclusion: SI increases the propensity to acquire and maintain psychostimulant intake Abbreviations: Ø: no difference; ↓: reduction; ↑: increase; ±: around CPP: Conditioned Place Preference; FR: fixed ratio; inf.: infusion; i.p.: intraperitoneal injection; L-E: Long-Evans; L-H: Lister-Hooded; P: post-natal day; PR: progressive ratio; SA: self-administration; S-D: Sprague-Dawley; SI: post-weaning social isolation rearing [1] Schenk, S et al., Pharmacol Biochem Behav, 1988 [2] Bozarth, M.A et al., Pharmacol Biochem Behav, 1989 [3] Phillips, G.D et al., Psychopharmacology (Berl), 1994 [4] Boyle, A.E et al., Pharmacol Biochem Behav, 1991 [5] Yajie, D et al., Pharmacol Biochem Behav, 2005 [6] Howes, S.R et al., Psychopharmacology (Berl), 2000 [7] Schenk, S et al., Neuroscience letters, 1987 [8] Baarendse, P.J et al., Psychopharmacology (Berl), 2014 [9] Arndt, D.L et al., Psychopharmacology (Berl), 2015 [10] Grotewold, S.K et al., Psychopharmacology (Berl), 2014 [11] 53 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Schenk, S et al., Pharmacol Biochem Behav, 1986 [12] Wongwitdecha, N., Marsden, C.A., Eur J Pharmacol, 1995 [13] Whitaker, L.R et al., Neuron, 2013 54 Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn C.33.44.55.54.78.65.5.43.22.2.4 22.Tai lieu Luan 66.55.77.99 van Luan an.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.C.33.44.55.54.78.655.43.22.2.4.55.22 Do an.Tai lieu Luan van Luan an Do an.Tai lieu Luan van Luan an Do an Stt.010.Mssv.BKD002ac.email.ninhd 77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77.77.99.44.45.67.22.55.77.C.37.99.44.45.67.22.55.77t@edu.gmail.com.vn.bkc19134.hmu.edu.vn.Stt.010.Mssv.BKD002ac.email.ninhddtt@edu.gmail.com.vn.bkc19134.hmu.edu.vn