The purpose of this research study was to determine the effects of Fostering Resilience™ (FR), a new integrative relapse prevention group protocol for improving relapse risk, internalized shame, and psychological well-being in adults with substance use disorders (SUD). This study also sought to identify any relationship among relapse risk, internalized shame, and psychological well-being. It is the first study to investigate the new FR manualized program model compared to treatment as usual (TAU). The FR model was created based upon direct client experience, the supposition of the intrinsic role shame plays in SUD, and the corresponding belief in the essential value of implementing shame reduction techniques for improving treatment outcomes. Participants were 43 adults with SUD (19 FR and 24 TAU) seeking outpatient treatment. All participants received the 8-week intensive outpatient (IOP) treatment, with the FR group receiving 16 sessions of the manualized FR relapse prevention group protocol in lieu of other TAU group options. Assessments were administered pre and postintervention. Results indicated that the FR treatment group produced a significant reduction in relapse risk (p = .002, ES = .825), shame (p = .004, ES = .763), and psychological wellbeing (p = .008, ES = .679) from baseline to post-intervention, while the TAU comparison group produced a non-significant improvement in relapse risk (p = .209, ES = .264), shame (p = 055, ES = .409) and psychological well-being (p = .088, ES = .456). Correlation results indicated highly significant correlations between all the dependent variables. All correlations dropped post-intervention, although remained significant. The strongest relationship was found between shame and relapse risk at baseline: ALL (n = 43, r = .880), FR (n = 19, r = .869), TAU (n = 24, r = .908). This preliminary study establishes support for the new FR model as a beneficial treatment for significantly improving relapse risk, internalized shame, and psychological well-being in adults with SUD. It also provides important knowledge and insight regarding the critical nature of shame and its role relative to relapse risk and psychological well-being in those with SUD. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

Females diagnosed with a substance use disorder (SUD) may experience more stigmatization and need more social support than males. Traditional therapeutic services provide interventions and treatment that is uniform for males and females. The available research on female substance users does not address meaningful connections and relationships with others, and its effect on overall wellness. The objective of this study was to address the importance of social support, stigmatization, and wellness. A sample of 232 females diagnosed with SUD, at least 18 years of age, responded to three instruments and a demographic form. The results of this study indicate that income and age are predictors of overall wellness and explained 12% of the variance in wellness, when using a multiple regression analysis, (adjusted R^2 = .119, p = .000). Relationship status and relationship length demonstrated significance as predictors of social support, explaining 5.6% of the variance in social support, using a multiple regression analysis, (adjusted R^2 = .056, p = .001). Number of children, age, and relationship length demonstrated significance as predictors of stigmatization, accounting for 9.4% of the variance in stigmatization, (adjusted R^2 = .094, p = .000). Social support accounted for 4.1% of the variance in stigmatization using a multiple regression analysis, (adjusted R^2 = .041, p = .001). Social support explained 39% of the variance in wellness, (adjusted R^2 = .394, p = .000). Using a hierarchical regression analysis to control for stigmatization, social support explained 44% of the variance in wellness, (adjusted R^2 = .438, p = .000). Finally, social support mediates the relationship between stigmatization and wellness, when using path analysis. This study provided support for specific treatment for females in substance abuse treatment; particularly concerning social support, stigmatization, and wellness. These females with SUD reported that social support increased wellness, correlating with decreased stigmatization. Conversely, females who experienced increased stigmatization and decreased social support also experienced decreased wellness. Social support mediated the impact of stigmatization and wellness. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

In recent years, food addiction has become a popular construct believed to have serious behavioral, emotional and physical consequences. However, its scientific validity is still under investigation. This dissertation evaluated whether food addiction is a valid mental disorder, substance-related disorder, and addiction in three parts. Part 1 reviewed the phenomenological, animal and neurological evidence to assess whether food addiction has face validity and conducted a systematic literature review of studies estimating the prevalence, validating measures, and/or assessing correlates of human food addiction to evaluate construct validity. Part 2 used two community-based convenience samples to assess whether operationalized measures of food addiction are reliable and valid. Part 3 used two large cohorts of nurses to evaluate whether food addiction is associated with potentially positively reinforcing nutrients, food items and food groups. The literature review established that food addiction has face validity, and to some degree, construct validity. The first analytic paper found that the internal and test-retest reliabilities of both scales were moderate to good, and the shorter Modified Yale Food Addiction Scale compared with the original Yale Food Addiction Scale had good sensitivity and negative predictive value. The second analytic paper found strong positive associations between food addiction and consumption of fats and sodium, non-sweet fatty foods, diet foods, and some salty and sweet foods, no association with most starchy and salty food items, and an inverse association with fruits and vegetables. It also found unexpected strong inverse associations between sugar and food addiction, contradicting the popular “sugar addiction” hypothesis. Prospective analyses should reexamine these findings to eliminate potential reverse causation bias. Taken together, this dissertation supported food addiction as a valid mental disorder, substance-related disorder and addiction, although some findings contradicted a priori hypotheses, and gaps in the literature remain.

In psychiatry, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is the standard classification system used by clinicians to diagnose disorders. The DSM provides criteria sets that are quantifiable and directly observable measures or symptoms associated with each disorder. For classification, a minimum number of criteria must be observed and once this threshold is met, a disorder is considered to be present. For some disorders, a dimensional classification is also provided by the DSM where severity of disorder increases as the number of criteria observed increases (i.e., None, Mild, Moderate and Severe). While the criteria sets provided by the DSM are the primary assessment mechanisms used by clinicians in psychiatric disease classification, some criteria sets may have too many items making them problematic and/or inefficient in clinical and research settings. In addition, psychiatric disorders are inherently latent constructs without any direct visual or biological observation available which makes validation of psychiatric diagnoses difficult. The present dissertation proposes and applies two empirical statistical methods to address lengthy criteria sets and validation of diagnoses. The first proposal is a data-driven method packaged as a SAS Macro that systematically identifies subsets of criteria and associated cut-offs (i.e., diagnostic short-forms) that yield diagnoses as similar as possible as using the full criteria set. The motivating example is alcohol use disorder (AUD) which is a type of substance use disorder (SUD) in the DSM-5. A diagnosis of AUD is made when two or more of the 11 possible criteria associated with it are observed. Relying on data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III), the new methodology identifies diagnostic short-forms for AUD by: (1) maximizing the association between the sum scores of all 11 criteria with newly constructed subscales from subsets of criteria, (2) optimizing the similarity of AUD prevalence between the current DSM-5 rule and newly constructed diagnostic short-forms, (3) maximizing sensitivity and specificity of the short-forms against the current DSM-5 rule, and (4) minimizing differences in the accuracy of the short-form across chosen covariates. The second method introduces external validators of disorder into the process of identifying and validating short-forms. Each step in the first methodology uses some type of comparison (i.e., maximizing correlation, sensitivity, specificity) with the current DSM rule assuming the DSM is the best diagnostic target to use. However, the method does not itself assess the validity of the criteria-based definition but instead relies on the validity of the original diagnosis. For the second methodology, we no longer assume the validity of the current DSM rule and instead introduce the use of external validators (antecedent, concurrent, and predictive) as the target when identifying short-forms. Application of the method is again AUD and the NESARC III is used as the data source. Rather than use the binary yes/no diagnosis, we use the dimensional classification framework provided by the DSM to identify and validate subsets and associated severity cut-offs (i.e., dimensional short-forms) in a systematic way. Using each external validator separately in the process could prove difficult in determining a consensus across the validators. Instead, our methodology offers a way to combine these external validators into a singular summary measure using factor analysis that derives the external composite validator (ECV). Using NESARC-III and following principles of convergent validity, we identify dimensional short-forms that most relate to the ECV in theoretically justified ways. Specifically, we obtain nested subsets of the original criteria set that (1) maximize the association between ECV and newly constructed subscales from subsets of criteria and (2) obtain associated severity cut-offs that maximally discriminate on ECV based on R-Squared. Substance use disorders in the DSM-5 include alcohol use disorder (AUD), nicotine use disorder (NUD) and drug use disorders (DUDs). Each of these substances is associated with a single underlying SUD construct with the same 11 diagnostic criteria used across each substance and the same diagnostic classifications. Cannabis and non-medical prescription opioids are two examples of DUDs and both have recently been identified as major public health priorities. Due to their diagnostic similarity to AUD in the DSM-5, these substances were ideal to also test our methodologies. Using data from the NESARC on criteria for cannabis use disorder (CUD) and opioid use disorder (OUD), we forward applied the diagnostic short-forms that accurately replicated AUD and also applied the methods to each substance separately. Overall, the new methodology was able to identify shorter criteria sets for AUD, CUD, and OUD that yielded highly accurate diagnosis compared to the current DSM (i.e., high sensitivity and specificity). Specifically, excluding criteria “Neglected major roles to use” and/or “Activities given up to use” created no marked change in ability to diagnose or measure severity the same way as DSM-5. When applying the method for identifying the most valid dimensional short-forms using external validators, different severity cut-points compared to the current DSM-5 were found and different cut-points were found across AUD, OUD, and CUD. There were dimensional short-forms with as few as 7 criteria for AUD, CUD and OUD that demonstrated the same or better level of validity as using all 11 criteria. We discuss the implications of these findings and propose recommendations for future DSM revisions. Lastly, we review limitations and future extensions of each of our proposed methodologies.

Wan Lei Nei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 126-160). / Abstract and questionnaires in English and Chinese. / Acknowledgement --- p.vi / Abstract --- p.vii / List of abbreviations --- p.xii / Chapter CHAPTER ONE --- INTRODUCTION --- p.1 / Chapter 1.1 --- Club drugs --- p.1 / Chapter 1.1.1. --- "Pattern of ""club drug"" use in Hong Kong" --- p.2 / Chapter 1.1.2. --- "Popular ""club drugs"" used in Hong Kong and their effects" --- p.4 / Chapter 1.1.2.1. --- MDMA ('ecstasy') --- p.4 / Chapter 1.1.2.2. --- Ketamine --- p.7 / Chapter 1.1.2.3. --- Cannabis --- p.10 / Chapter 1.1.2.4. --- Methamphetamine ´(بIce'） --- p.12 / Chapter 1.2 --- Neurobiology of drug addiction --- p.13 / Chapter 1.2.1 --- Introduction to reward pathways and animal models of addiction --- p.13 / Chapter 1.2.2 --- Mesocorticolimbic dopamine pathway --- p.15 / Chapter 1.2.3 --- Behavioural processes of addiction --- p.18 / Chapter 1.2.4 --- Other neurotransmitter systems in addiction --- p.21 / Chapter 1.2.5 --- Molecular plasticity in addiction: signaling and gene expression --- p.23 / Chapter 1.3 --- Association of Personality Traits and Drug Abuse --- p.26 / Chapter 1.4. --- Association between genetics and drug abuse --- p.31 / Chapter 1.4.1 --- "Family, twin and adoption studies" --- p.32 / Chapter 1.4.2 --- Transgenic and knock out animal models --- p.33 / Chapter 1.4.3 --- Candidate genes for drug abuse --- p.33 / Chapter 1.4.3.1 --- Dopamine receptor genes --- p.34 / Chapter 1.4.3.2 --- Monoamine Oxidase (MAO) gene --- p.35 / Chapter 1.4.3.3 --- Catechol-O-methyltransferase (COMT) gene --- p.35 / Chapter 1.4.3.4 --- Serotonergic genes --- p.37 / Chapter 1.4.3.5 --- Opioid receptor genes --- p.38 / Chapter 1.4.4 --- Linkage studies of drug abuse --- p.39 / Chapter 1.5 --- Genetic factor and personality trait --- p.39 / Chapter 1.5.1 --- Twins study --- p.41 / Chapter 1.5.2 --- Candidate gene studies --- p.41 / Chapter 1.5.3.1 --- Dopamine (DA) --- p.42 / Chapter 1.5.3.2 --- COMT --- p.43 / Chapter 1.5.3.3 --- MAO-A --- p.44 / Chapter 1.5.3.4 --- Serotonin (5-HT) --- p.44 / Chapter 1.5.3.5 --- Opioid receptor --- p.46 / Chapter 1.5.4 --- Interaction between genes --- p.47 / Chapter 1.6 --- Aim of study --- p.47 / Chapter CHAPTER TWO --- MATERIALS AND METHODS --- p.50 / Chapter 2.1 --- Recruitment of Subjects --- p.50 / Chapter 2.1.1. --- Club drug users --- p.50 / Chapter 2.1.2. --- Controls --- p.50 / Chapter 2.2 --- Phenotype assessment --- p.51 / Chapter 2.2.1 --- Questionnaire (Appendix la 226}0ؤ Chinese version used; lb - English translated version for reference only) --- p.51 / Chapter 2.2.1.1 --- Demographics --- p.51 / Chapter 2.2.1.2 --- Pattern of drug use --- p.52 / Chapter 2.2.1.3 --- First time drug use --- p.52 / Chapter 2.2.1.4 --- Reason of drug use --- p.52 / Chapter 2.2.1.5 --- Effects of drug use --- p.52 / Chapter 2.2.1.6 --- Potential dependence/ withdrawal --- p.53 / Chapter 2.2.1.7 --- Knowledge about drug of abuse and psychological well-being. --- p.53 / Chapter 2.2.2 --- Personality assessments (Appendix 2a - Chinese version of SSS-V scale; 2b -Chinese version of BIS/BAS scale) --- p.53 / Chapter 2.3 --- DNA extraction --- p.53 / Chapter 2.4 --- Genotyping --- p.54 / Chapter 2.4.1 --- "G1947A, Val108/158 Met polymorphism in the catechol-O-methyltransferase (COMT) gene" --- p.55 / Chapter 2.4.2 --- T941G polymorphism in the monoamine oxidase A (MAO-A) gene --- p.55 / Chapter 2.4.3 --- TaqI A Polymorphism of the DRD2 Gene --- p.56 / Chapter 2.4.4 --- 7-repeat allele of a 48 bp repeat polymorphism (DRD4-7) in exon 3 of the dopamine D4 receptor gene (DRD4) --- p.57 / Chapter 2.4.5 --- -521C/T single nucleotide polymorphism (SNP) I the promoter region of the dopamine D4 receptor gene (DRD4) --- p.58 / Chapter 2.4.6 --- G861C polymorphism in the serotonin receptor 1B (5-HT1B) gene --- p.59 / Chapter 2.4.7 --- The 44 bp insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) --- p.60 / Chapter 2.4.8 --- T921C Polymorphism in Exon 3 of the Human DOR (hDOR) Gene --- p.60 / Chapter 2.4.9 --- A118G polymorphism in Exon 1 of the Human MOR (hMOR) Gene --- p.61 / Chapter 2.5 --- DNA sequencing --- p.62 / Chapter 2.6 --- Statistical Analysis --- p.63 / Chapter CHAPTER THREE --- RESULTS --- p.65 / Chapter 3.1 --- Results from questionnaire --- p.65 / Chapter 3.1.1 --- Demographics of club drug users --- p.65 / Chapter 3.1.1.1 --- Gender and age --- p.65 / Chapter 3.1.1.2 --- District of residence --- p.65 / Chapter 3.1.1.3 --- Type of living quarters and cohabitation --- p.65 / Chapter 3.1.1.4 --- Educational attainment and employment status --- p.66 / Chapter 3.1.1.5 --- Parents'details --- p.66 / Chapter 3.1.2 --- First time drug use --- p.67 / Chapter 3.1.3 --- Prevalence of drug use --- p.68 / Chapter 3.1.4 --- Frequency and quantity of drug used --- p.69 / Chapter 3.1.7 --- Drug spending --- p.70 / Chapter 3.1.8 --- Pattern of drug use in and outside Hong Kong --- p.71 / Chapter 3.1.9 --- Cause of drug use --- p.75 / Chapter 3.1.10 --- The negative effects of drug use --- p.77 / Chapter 3.1.11. --- Potential tolerance/ dependence --- p.79 / Chapter 3.1.12 --- Knowledge about drugs of abuse --- p.80 / Chapter 3.1.13 --- Psychological well-being --- p.80 / Chapter 3.2 --- Personality trait assessments --- p.81 / Chapter 3.2.1 --- Personality traits between club drugs users and controls --- p.81 / Chapter 3.2.2 --- Personality trait by gender --- p.81 / Chapter 3.2.3 --- Reliability --- p.83 / Chapter 3.3 --- Genotyping --- p.84 / Chapter 3.3.1 --- "G1947A,Vall08/158 Met polymorphism in the catechol-O-methyl- transferase (COMT) gene" --- p.84 / Chapter 3.3.2 --- T941G polymorphism in the monoamine oxidase A (MAO-A) --- p.87 / Chapter 3.3.3 --- T921C Polymorphism in Exon 3 of the Human DOR (hDOR) Gene --- p.90 / Chapter 3.3.4 --- G861C polymorphism in the serotonin receptor 1B (5-HT1B) gene --- p.92 / Chapter 3.3.5 --- TaqI A Polymorphism of the DRD2 Gene --- p.94 / Chapter 3.3.6 --- The All 8G polymorphism in exon 1 of the human MOR (hMOR) gene --- p.96 / Chapter 3.3.7 --- The 44 bp insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) --- p.97 / Chapter 3.3.8 --- 48bp repeat polymorphism (DRD4) in exon 3 of the dopamine D4 receptor gene (DRD4) --- p.98 / Chapter 3.3.9 --- -521C/T polymorphism in the promoter region of the dopamine D4 receptor gene (DRD4) --- p.99 / Chapter CHAPTER FOUR --- DISCUSSION --- p.100 / Chapter 4.1 --- Demographics and pattern of club drug use --- p.100 / Chapter 4.2 --- Personality traits assessment --- p.108 / Chapter 4.3 --- Gene polymorphisms --- p.110 / Chapter 4.3.1 --- "COMT G1947A, Val108/158 Met polymorphism" --- p.111 / Chapter 4.3.2. --- MAO-A T941G polymorphism --- p.114 / Chapter 4.3.3. --- hDOR T921C polymorphism --- p.115 / Chapter 4.3.4. --- hMOR A118G polymorphism --- p.117 / Chapter 4.3.5 --- DRD2 TaqI A polymorphism --- p.118 / Chapter 4.3.6 --- DRD4 48bp VNTR polymorphism --- p.120 / Chapter 4.3.7. --- DRD4 -C521T polymorphism --- p.121 / Chapter 4.3.8. --- 5-HT1B G861C polymorphism --- p.121 / Chapter 4.3.9. --- 5-HTTLPR SLC6A4 44 bp insertion/deletion polymorphism --- p.122 / REFERENCES --- p.125 / APPENDIX 1a Questionnaire (Chinese version) / APPENDIX 1b Questionnaire (English translated version) / APPENDIX 2a Chinese version of SSS-V scale / APPENDIX 2b Chinese version of BIS/BAS scale

Magister Psychologiae - MPsych / There are many theories as to why adolescents engage in substance abuse. These theories have formed the basis of various substance abuse prevention programmes aimed at reducing this problem. Evaluation of these interventions is needed in order to assess their effectiveness and to improve on future prevention strategies. The literature highlights tensions and differences between the primary preventative approaches to substance abuse and the harm reduction model. It also suggests that psychosocial or life skills programmes and interventions employing a harm reduction approach tend to be viewed as more suitable for adolescents than other approaches. This study focuses on a high school intervention programme running since 1996, which has not yet been evaluated. It aimed to identify the programme's strengths and weaknesses, as well as participants' perception of the intervention. A qualitative research method was used, employing focus groups as the tool for data gathering. The sample for the study was made up of 30 volunteers from three grade 10 classes that completed the programme two years prior to this study. Data was transcribed verbatim and analyzed using thematic analysis. Links were made to the two approaches referred to above. Analysis of the data indicated that although stories used to warn and frighten people were shown to have a shocking impact on the participants, pupils found it difficult to make the connection between the speakers' horrific stories and their own experimentation with drugs and alcohol. It was found that participants appreciated the fact that they were being informed about the dangers of substance use, and that they were encouraged to take responsibility for their own decisions regarding this behaviour. The informal, non-judgemental stance of the speakers served to reinforce this message. In conclusion, the study indicated that the different methods used in the various prevention programmes are in fact not altogether different. It is suggested that the various models are potentially compatible, and can perhaps work together to establish an effective preventative strategy.

Impulsivity, venturesomeness, and pride variables were examined as potential moderators of the associations between childhood trauma and physical aggression, alcohol use and physical aggression, and drug use and physical aggression. Participants (n = 457) were college students recruited from a university in the Southeast. It was hypothesized that childhood trauma, alcohol use, and drug use would be associated with increased scores of physical aggression. In addition, it was hypothesized that impulsivity, venturesomeness, authentic pride, and hubristic pride would moderate these relationships. Linear, multivariate hierarchical regression analyses were used to examine these variables as potential moderators. Hypotheses concerning hubristic pride as a moderator of the relationship between alcohol use and physical aggression as well as the relationship between drug use and physical aggression were supported. In addition, the hypothesis concerning authentic pride as a moderator of the relationship between alcohol use and physical aggression was supported albeit in the opposite direction than predicted. Hypotheses concerning the moderating roles of impulsivity and venturesomeness were not supported. Findings support the idea that the deleterious psychological effects of substance use can be compounded by personality factors such as authentic and hubristic pride. The discussion encompasses why interventions should target attributions and cognitions and why simply encouraging someone to have a more “healthy pride” is likely to be ineffective at reducing physical aggression in the context of drug use and alcohol use.

Our lab has shown that neonatal treatment with quinpirole, a dopamine D2/D3 agonist, to rats resulted in an increase in dopamine D2‐like receptor sensitivity that persists throughout the animal’s lifetime without a change in receptor number, consistent with schizophrenia. Approximately 80‐85% of schizophrenics smoke cigarettes, and there is no delineated mechanism for this observation. Our lab has also shown more robust sensitization and accumbal dopamine release in response to nicotine in adolescent rats neontally treated with quinpirole compared to controls. This study analyzed whether environmental enrichment, known to reduce sensitization to psychostimulants, may also reduce or block enhanced sensitization to nicotine in this model. Male and female rats were treated with either quinpirole (1 mg/kg) or saline from postnatal day (P)1‐21. After weaning at P21, animals were raised in either environmentally enriched or isolated housing throughout the experiment. Beginning on P33, animals were ip administered either nicotine (0.5 mg/kg free base) or saline 10 min before placement in a square locomotor arena and behavioral activity measured every second day from P33‐49. Results revealed that animals given neonatal quinpirole treatment and reared in an enriched environment demonstrated more robust sensitization to nicotine than all other groups. Animals given neonatal quinpirole or saline treatment followed by nicotine in adolescence and raised in isolated housing conditions were equivalent, but demonstrated more robust sensitization compared to enriched rats Page 13 of 35 neonatally treated with saline and administered nicotine in adolescence. Results here show that environmental enrichment enhanced nicotine sensitization in rats neonatally treated with quinpirole, which is in contrast to the blockade of sensitization to nicotine which has previously been shown in normal animals. Importantly, these results show that increases in D2 receptor sensitivity interacts with environmental enrichment differently than in normal animals and the manner in which the animal responds to nicotine, which may have implications towards smoking cessation in schizophrenia.

Aims: Neonatal quinpirole (a dopamine D2-like agonist) treatment to rats has been shown to increase dopamine D2 receptor sensitivity throughout the animal’s lifetime, and increased dopamine D2 sensitivity is a hallmark of schizophrenia. Schizophrenics are 3 to 4 times more likely to smoke than the normal population, but there is no delineating mechanism. Aim 1: Behaviorally test a rewarding versus averisve dose of nicotine in adolescent rats neonatally treated with quinpirole tested in a place preference paradigm; Aim 2: Analyze phosphorylated cylic AMP response element bidning protein (CREB) in brain areas that mediate drug reward. Methods: Rats were neonatally treated with quinpirole from postnatal days (P)1- 21. After two drug free preferene tests were given in a place preference shuttle box at P41-42, animals were conditioned with saline, a 0.6 or a 1.8 mg/kg free base dose of nicotine for eight consecutive days. A post-conditioning test was given 24 h after conditioning. Time in the paired and unpaired context were measured. Approximately 24 h after the post-condioning test, brain tissue was harvested, flash frozen, and later analyzed for pCREB in the dorsal and nucleus accumbens. Results: Results revealed that neonatal quinpirole enhanced the rewarding associative effects of the lower dose of nicotine compared to animals neonatally treated with saline and conditioned with the same dose of nicotine, which showed a slight place preference. Interestingly, although neonatal saline animals conditioned with the higher dose of nicotine demonstrated conditioned place aversion, neonatal quinpirole treated animals demonstrated no aversion to this same dose. Analyses for p-CREB will be presented. Conclusions: Rats neonatally treated with quinpirole demonstrate an enhancement of the rewarding properties of nicotine, but do not demonstrate an aversion to higher doses of nicotine. These data are congruent with recent self-administration data in our lab, and suggest that increases of dopamine D2 sensitivity may blunt aversive aspects of nicotine.

Our lab has shown that neonatal treatment with quinpirole, a dopamine D2/D3 agonist, to rats resulted in an increase in dopamine D2-like receptor sensitivity that persists throughout the animal’s lifetime without a change in receptor number, consistent with schizophrenia. Approximately 80-85% of schizophrenics smoke cigarettes, and there is no delineated mechanism for this observation. Our lab has also shown more robust sensitization and accumbal dopamine release in response to nicotine in adolescent rats neontally treated with quinpirole compared to controls. This study analyzed whether environmental enrichment, known to reduce sensitization to psychostimulants, may also reduce or block enhanced sensitization to nicotine in this model. Male and female rats were treated with either quinpirole (1 mg/kg) or saline from postnatal day (P)1-21. After weaning at P21, animals were raised in either environmentally enriched or isolated housing throughout the experiment. Beginning on P33, animals were ip administered either nicotine (0.5 mg/kg free base) or saline 10 min before placement in a square locomotor arena and behavioral activity measured every second day from P33-49. Results revealed that animals given neonatal quinpirole treatment and reared in an enriched environment demonstrated more robust sensitization to nicotine than all other groups. Animals given neonatal quinpirole or saline treatment followed by nicotine in adolescence and raised in isolated housing conditions were equivalent, but demonstrated more robust sensitization compared to enriched rats neonatally treated with saline and administered nicotine in adolescence. Results here show that environmental enrichment enhanced nicotine sensitization in rats neonatally treated with quinpirole, which is in contrast to the blockade of sensitization to nicotine which has previously been shown in normal animals. Importantly, these results show that increases in D2 receptor sensitivity interacts with environmental enrichment differently than in normal animals and the manner in which the animal responds to nicotine, which may have implications towards smoking cessation in schizophrenia.