Abstract available through American Journal of Epidemiology.

Abstract available through Clinical Pharmacology in Drug Development.

Schizophrenics are significantly more likely to smoke cigarettes than the general population. In Experiment 1, we analyzed the effects of a rewarding versus an aversive dose of nicotine using the neonatal quinpirole (QUIN; dopamine D2/D3 agonist) model of schizophrenia. In Experiment 2, we examined the effects of antipsychotic treatment upon the associative reward of nicotine within this same model. Neonatal QUIN treatment to rats results in increased dopamine D2 receptor sensitivity throughout the rat’s lifetime, consistent with schizophrenia. Rats were neonatally treated with QUIN (1 mg/kg dose) or saline from postnatal days (P)1-21. Animals were then raised to P41 without any further drug treatment. Subjects were administered two consecutive pre-conditioning drug free preference tests in a three chamber shuttle box on P41 and P42 to determine initial preference. In Experiment 1, beginning on P43, animals were conditioned with saline, a 0.6 mg/kg or a 1.8 mg/kg free base dose of nicotine for eight consecutive days. A drug free post-conditioning preference test was given on P51. Approximately 24 h following the post-conditioning test, brain tissue was harvested and analyzed for mammalian target of rapamycin (mTOR) and phosphorylated-CREB (pCREB) in the nucleus accumbens. In Experiment 2, animals were treated identically as in Experiment 1, but were conditioned with nicotine which was preceded by an injection of either a typical antipsychotic (haloperidol, 0.5 mg/kg dose) or an atypical antipsychotic (clozapine, 2.5 mg/kg dose) for a period of eight days which was followed by a drug free preference test. In both experiments, the difference between time spent in the paired context between pre-test and post-test was utilized as a measure of associative reward. Results revealed that neonatal QUIN enhanced the rewarding effects of nicotine, but neutralized the aversive effects compared to controls. Neonatal QUIN also significantly decreased accumbal mTOR and pCREB results will be presented. In Experiment 2, we found that treatment with clozapine reduced the enhancement of nicotine conditioned place preference, but haloperidol completely reduced nicotine place preference to control levels. These findings show that neonatal QUIN enhances the rewarding associative effects of nicotine, and that the typical antipsychotic haloperidol was more effective at eliminating the associative rewarding effects of nicotine likely due to its potent D2 antagonistic effects.

Abstract available through American Journal of Epidemiology.

Abstract available through Clinical Pharmacology in Drug Development.

Many patients suffering from depressive disorders are refractory to treatment with currently available antidepressant medications, while many more exhibit only a partial response. These factors drive research to discover new pharmacological approaches to treat depression. Numerous studies demonstrate evidence of inflammation and elevated oxidative stress in major depression. Recently, major depression has been shown to be associated with elevated levels of DNA oxidation in brain cells, accompanied by increased gene expression of the nuclear base excision repair enzyme, poly(ADP-ribose) polymerase-1. Given these findings and evidence that drugs that inhibit poly(ADP-ribose) polymerase-1 activity have antiinflammatory and neuroprotective properties, the present study was undertaken to examine the potential antidepressant properties of poly(ADP-ribose) polymerase inhibitors.

This study was designed to analyze the effects of adolescent exposure to methylphenidate (MPH; trade name: Ritalin) on nicotine self-administration, the motivation to obtain nicotine, and accumbal neuronal firing rate in female adolescent rats. MPH is the most commonly prescribed medication for Attention Deficit-Hyperactivity Disorder (ADHD) which is diagnosed in 3-5% of adolescents in the United States. However, this disorder is often misdiagnosed, and MPH is often prescribed to individuals not diagnosed with ADHD. Adolescent female Sprague-dawley rats were ip administered 1 mg/kg MPH or saline using a “school day” regimen of five days on, two days off, beginning on postnatal day (P)28 and this regimen was maintained throughout testing. A 1 mg/kg dose of MPH has been shown to result in brain plasma levels equivalent to clinical dosing in humans. Indwelling catheters were implanted in the jugular vein at P35, and one week later on P42, animals began nicotine self-administration. MPH (1 mg/kg) was administered each day approximately 6 h before each self-administration session began, which allows for nearly full plasma clearance of MPH (half-life = 1 h) before self-administration commenced. Rats were reduced to 85% of their free-feeding body weight and sipper tubes were made available to the rats in this paradigm, and responses to licking the tube produced an infusion of nicotine solution (15μg/kg) over a range of fixed ratio (FR) reinforcement schedules followed by a progressive ratio (PR) schedule, a measure of motivation. The schedule of reinforcement during 60 min sessions was increased from an FR5 to FR15 over approximately a three-week period. Results revealed that MPH pre-exposed rats self-administered significantly higher amounts of nicotine as compared to animals treated with saline throughout the FR5 and FR10 schedules. Further, MPH enhanced the motivation to self-administer nicotine on the PR schedule compared to controls, demonstrating an enhanced motivation to obtain nicotine produced by MPH. Finally, animals that had been pre-exposed to MPH and self-administered nicotine demonstrated a lower rate of basal accumbal firing as compared to controls, but a burst firing in response to nicotine that was higher than rats pre-exposed to saline. In conclusion, MPH altered the behavioral and neural response to nicotine in the nucleus accumbens.

Methylphenidate (MPH) is widely prescribed during childhood and adolescence for treatment of attention deficit and hyperactivity disorder. MPH is also one of the most commonly abused prescription drugs. However, the effects of MPH exposure and MPH abuse on incentive motivation are not well known. Moreover, MPH abuse during adolescence could increase sensitivity to the incentive motivational effects of other abused drugs such as nicotine in adulthood. Thus, the goals of this experiment were to investigate the effects of MPH exposure on the motivation to obtain sucrose during adolescence and to examine whether adolescent methylphenidate exposure altered the incentive motivational effects of nicotine (NIC) in adulthood. Incentive motivation was measured using an operant conditioning paradigm with sucrose available under a progressive ratio schedule of reinforcement (PR). Adolescent female rats were used because our previous studies have shown stronger sensitization to the locomotor stimulant effects of MPH. Rats arrived at post-natal day 21 (P21) and were shaped to respond for sucrose (20% w/v) on the PR schedule beginning on P24. After stable operant responding was established, rats were randomly assigned to receive either MPH (n=7) or SAL (n=6) injections (intraperitoneal) 30 min prior to test sessions, with the constraint that sucrose rewards earned did not differ between groups. Injection tests began on P36 and were carried out on alternating days for 10 total tests (P36-54). Although there was a trend for increased motivation for sucrose in the MPH group, it did not reach statistical significance. No further testing occurred until the rats reached adulthood (P55-P78). Over the next 5 days (P79-P84), all rats were pretreated with subcutaneous NIC injections (0.4 mg/kg base) 15 min before testing sessions. Following this initial ‘sensitization’ period, rats were tested with different NIC doses (0-1 mg/kg base) from P85-P92. During the sensitization period, NIC increased responding equally in both groups. However, during the dose-response testing, rats in the MPH group were more sensitive to the incentive motivational effects of NIC - the median effective dose was significantly lower for rats exposed to MPH in adolescence. The findings suggest that MPH may have limited reinforcement enhancing effects in adolescents. However, exposure to MPH during adolescents may increase the incentive motivational effects of NIC in adulthood.

Magister Artium (Social Work) - MA(SW) / Substance abuse remains a debilitating social issue for many people in South Africa. It generally has a devastating effect on family life, and especially so when adolescents become dependent on substances, as it can have an adverse impact on their development. Interventions with adolescents include dealing with often complex developmental issues, dependence on family, and their support, which requires therapists to have special skills and patience to engage them in often complex treatment outcomes. The parent of a substance abusing adolescent is considered a role player in the aftercare of a substance abuse treatment programme as defined by the Prevention of and Treatment for Substance Abuse Act, 70 of 2008. The role of the parent is defined by their ability to monitor and supervise the adolescent and susceptible they are to adapt their parenting style to the suit the developmental needs of the child. The study sought to explore and describe the dynamics involved with parents and adolescents who have been through such a programme and how that can be utilised to influence their sobriety. This qualitative study, embedded in an exploratory descriptive research design, explored the role of the parent in the aftercare of their adolescent children who participated in a treatment programme for substance abuse. The population for this study included parents of adolescents who participated in a treatment programme for substance abuse and living in Port Elizabeth, Uitenhage and Despatch, in the Eastern Cape Province of South Africa. Purposive sampling was utilised to access 17 participants, and focus group, group and individual interviews were conducted as the data collection methods. The research interviews were transcribed and thematically analysed according to Moustakas (1994), and nine main themes emerged. The findings of the study will inform service providers and organs of State regarding the services needed to ensure continued support for adolescents who have been abusing substances. The main themes relating to the goal of the study were understanding the term ‘aftercare’, reflections on why adolescents were abusing substances, reflecting on experiences while the adolescent was abusing substances, parents’ experiences after the adolescent returned home, expectations of adolescents after treatment, parents’ views of what the adolescent in recovery needs, parental roles and responsibilities in recovery, informal support to the adolescent and his/her parents and descriptions of social workers in aftercare.

Military veterans are disproportionately represented in United States (U.S.) jails and prisons, with nearly 10% of current inmates being veterans. Veterans’ criminal justice involvement is often precipitated by underlying mental health and substance abuse that are connected to their military service. Veterans’ treatment courts are the judicial response to a need for more coordinated provision of mental health and substance abuse services to veterans involved in the criminal justice system. Modeled after drug courts and mental health courts, veterans treatment courts are a judicial innovation that aim to honor the service of veterans by providing them an alternative to incarceration. There are currently 551 veterans’ treatment courts in 42 states throughout country, including five in Kentucky. This exploratory descriptive study uses Andersen’s healthcare utilization model and a social control theoretical perspective as a framework to examine veterans’ treatment court outcomes from a sample of participants (N=58) in Kentucky. Univariate and bivariate analyses were used to provide a description of the sample and to examine relationships between personal characteristics and during-program occurrences and the outcomes of program completion and criminal recidivism. The findings of this study indicate that gender, sanctions, drug screens, and treatment sessions each have a significant association with program completion, and both age and housing status have a significant association with recidivism. Findings for each outcome variable are discussed, along with possible explanations, as well as limitations of the study, implications of this research for social work practice, and suggestions for future research.