Differential Regulation of the Period Genes in Striatal Regions Following Cocaine Exposure.

Differential Regulation of the Period Genes in Striatal Regions following Cocaine Exposure.

PLoS One. 2013; 8(6): e66438
Falcon E, Ozburn A, Mukherjee S, Roybal K, McClung CA

Several studies have suggested that disruptions in circadian rhythms contribute to the pathophysiology of multiple psychiatric diseases, including drug addiction. In fact, a number of the genes involved in the regulation of circadian rhythms are also involved in modulating the reward value for drugs of abuse, like cocaine. Thus, we wanted to determine the effects of chronic cocaine on the expression of several circadian genes in the Nucleus Accumbens (NAc) and Caudate Putamen (CP), regions of the brain known to be involved in the behavioral responses to drugs of abuse. Moreover, we wanted to explore the mechanism by which these genes are regulated following cocaine exposure. Here we find that after repeated cocaine exposure, expression of the Period (Per) genes and Neuronal PAS Domain Protein 2 (Npas2) are elevated, in a somewhat regionally selective fashion. Moreover, NPAS2 (but not CLOCK (Circadian Locomotor Output Cycles Kaput)) protein binding at Per gene promoters was enhanced following cocaine treatment. Mice lacking a functional Npas2 gene failed to exhibit any induction of Per gene expression after cocaine, suggesting that NPAS2 is necessary for this cocaine-induced regulation. Examination of Per gene and Npas2 expression over twenty-four hours identified changes in diurnal rhythmicity of these genes following chronic cocaine, which were regionally specific. Taken together, these studies point to selective disruptions in Per gene rhythmicity in striatial regions following chronic cocaine treatment, which are mediated primarily by NPAS2. HubMed – addiction


Relationship of food addiction to weight loss and attrition during obesity treatment.

Obesity (Silver Spring). 2013 Jun 14;
Lent MR, Eichen DM, Goldbacher E, Wadden TA, Foster GD

Objective: This study prospectively examined the relationship between food addiction (FA) and weight and attrition outcomes in overweight and obese adults participating in weight loss interventions. Design and Methods: Participants were 178 adults (51.2±11.7 y, 36.1±4.8 kg/m(2) ) in one of two outpatient weight-loss treatment programs for approximately six months. The Yale Food Addiction Scale (YFAS) assessed FA diagnosis and symptom count. The relationship between FA and weight loss and attrition was assessed. Results: After controlling for treatment arm, gender and baseline weight, there was no effect of FA status on weight loss (p=0.17) or attrition (p=0.37). Similarly, baseline FA symptom count was not associated with weight loss (p=0.14) or attrition (p=0.10). Conclusions: Neither FA status nor symptom count affects weight loss or attrition during weight loss treatment. HubMed – addiction


Placebo- and Amitriptyline-Controlled Evaluation of Central Nervous System Effects of the NK1 Receptor Antagonist Aprepitant and Intravenous Alcohol Infusion at Pseudo-Steady State.

J Clin Pharmacol. 2013 Jun 18;
Te Beek ET, Tatosian D, Majumdar A, Selverian D, Klaassen ES, Petty KJ, Gargano C, van Dyck K, McCrea J, Murphy G, van Gerven JM

Recent interest in NK1 receptor antagonists has focused on a potential role in the treatment of drug addiction and substance abuse. In the present study, the potential for interactions between the NK1 receptor antagonist aprepitant and alcohol, given as an infusion at a target level of 0.65?g/L, was evaluated. Amitriptyline was included as positive control to provide an impression of the profile of central nervous system (CNS) effects. In a double-blind, randomized, placebo- and amitriptyline-controlled study, the pharmacokinetics and CNS effects of aprepitant and alcohol were investigated in 16 healthy volunteers. Cognitive and psychomotor function tests included the visual verbal learning test (VVLT), Bond and Lader visual analogue scales (VAS), digit symbol substitution test (DSST), visual pattern recognition, binary choice reaction time, critical flicker fusion (CFF), body sway, finger tapping, and adaptive tracking. Alcohol impaired finger tapping and body sway. Amitriptyline impaired DSST performance, VAS alertness, CFF, body sway, finger tapping, and adaptive tracking. No impairments were found after administration of aprepitant. Co-administration of aprepitant with alcohol was generally well tolerated and did not cause significant additive CNS effects, compared with alcohol alone. Therefore, our study found no indications for clinically relevant interactions between aprepitant and alcohol. HubMed – addiction


Buprenorphine Use in Pregnant Opioid Users: A Critical Review.

CNS Drugs. 2013 Jun 18;
Soyka M

Pregnancy in opioid users poses a number of problems to treating physicians. Most guidelines recommend maintenance treatment to manage opioid addiction in pregnancy, with methadone being the gold standard. More recently, buprenorphine has been discussed as an alternate medication. The use and efficacy of buprenorphine in pregnancy is still controversial. This article reviews the current database on the basis of a detailed and critical literature search performed in MEDLINE (206 counts). Most of the relevant studies (randomised clinical trials and one national cohort sample) were published in the last 2 years and mainly compared buprenorphine with methadone. Some studies are related to maternal outcomes, others to foetal, neonatal or older child outcomes. With respect to maternal outcomes, most studies suggest that buprenorphine has similar effects to methadone. Very few data from small studies discuss an effect of buprenorphine on neurodevelopment of the foetus. Neonatal abstinence syndrome is common in infants of both buprenorphine- and methadone-maintained mothers. As regards neonatal outcomes, buprenorphine has the same clinical outcome as methadone, although some newer studies suggest that it causes fewer withdrawal symptoms. Since hardly any studies have investigated the combination of buprenorphine with naloxone (which has been suggested to possibly have teratogenic effects) in pregnant women, a switch to buprenorphine monotherapy is recommended in women who become pregnant while receiving the combination product. These novel findings indicate that buprenorphine is emerging as a first-line treatment for pregnant opioid users. HubMed – addiction


Substance Abuse and Smoking Among a Canadian Cohort of First Episode Psychosis Patients.

Community Ment Health J. 2013 Jun 18;
Deruiter WK, Cheng C, Gehrs M, Langley J, Dewa CS

Individuals experiencing their first psychotic episode report rates of substance and tobacco use that are higher than observed in the general population. In this sample of individuals diagnosed with first episode psychosis, rural/non-rural variations in substance use and smoking behaviour were evaluated. Analyses were performed utilizing data from a sample of individuals enrolled in early intervention programs located throughout the province of Ontario. Based upon population density, two geographical regions were developed: rural and non-rural. Illicit drug use, alcohol consumption, and smoking behaviour were assessed. The total sample consisted of 152 individuals experiencing their first episode of psychosis. Of these individuals, 82 and 70 resided in rural and non-rural areas, respectively. Rural vs non-rural residence was not significantly associated with substance or tobacco use. Regardless of geographical location, early intervention programs for individuals experiencing their first psychotic episode need to incorporate interventions that address substance use. HubMed – addiction