Cannabinoid Receptor 1-Expressing Neurons in the Nucleus Accumbens.

Cannabinoid receptor 1-expressing neurons in the nucleus accumbens.

Filed under: Addiction Rehab

Proc Natl Acad Sci U S A. 2012 Sep 10;
Winters BD, Krüger JM, Huang X, Gallaher ZR, Ishikawa M, Czaja K, Krueger JM, Huang YH, Schlüter OM, Dong Y

Endocannabinoid signaling critically regulates emotional and motivational states via activation of cannabinoid receptor 1 (CB1) in the brain. The nucleus accumbens (NAc) functions to gate emotional and motivational responses. Although expression of CB1 in the NAc is low, manipulation of CB1 signaling within the NAc triggers robust emotional/motivational alterations related to drug addiction and other psychiatric disorders, and these effects cannot be exclusively attributed to CB1 located at afferents to the NAc. Rather, CB1-expressing neurons in the NAc, although sparse, appear to be critical for emotional and motivational responses. However, the cellular properties of these neurons remain largely unknown. Here, we generated a knock-in mouse line in which CB1-expressing neurons expressed the fluorescent protein td-Tomato (tdT). Using these mice, we demonstrated that tdT-positive neurons within the NAc were exclusively fast-spiking interneurons (FSIs). These FSIs were electrically coupled with each other, and thus may help synchronize populations/ensembles of NAc neurons. CB1-expressing FSIs also form GABAergic synapses on adjacent medium spiny neurons (MSNs), providing feed-forward inhibition of NAc output. Furthermore, the membrane excitability of tdT-positive FSIs in the NAc was up-regulated after withdrawal from cocaine exposure, an effect that might increase FSI-to-MSN inhibition. Taken together with our previous findings that the membrane excitability of NAc MSNs is decreased during cocaine withdrawal, the present findings suggest that the basal functional output of the NAc is inhibited during cocaine withdrawal by multiple mechanisms. As such, CB1-expressing FSIs are targeted by cocaine exposure to influence the overall functional output of the NAc.
HubMed – addiction

 

Operant psychostimulant self-administration in a rat model of depression.

Filed under: Addiction Rehab

Pharmacol Biochem Behav. 2012 Sep 22;
Lin SJ, Epps SA, West CH, Boss-Williams KA, Weiss JM, Weinshenker D

Depression and psychostimulant addiction are co-morbid conditions; depression is a significant risk factor for psychostimulant abuse, and the rate of depression in drug addicts is higher than in the general population. Despite the prevalence of this comorbidity, there are few animal models examining psychostimulant abuse behaviors in depression. We have shown previously that while rats selectively bred for depression-like phenotypes (SwLo) have blunted mesolimbic dopamine (DA) signaling and locomotor responses to dopaminergic drugs, they voluntarily administer excessive amounts of psychostimulants compared to normal or depression-resistant (SwHi) rats in oral consumption paradigms. To determine whether this increased drug intake by depression-sensitive rats extends to operant self-administration, we assessed fixed ratio-1, progressive ratio, extinction, and reinstatement responding for cocaine and amphetamine in SwLo and SwHi rats. Contrary to the oral consumption results, we found that the SwHi rats generally responded more for both cocaine and amphetamine than the SwLo rats in several instances, most notably in the progressive ratio and reinstatement tests. Food-primed reinstatement of food seeking was also elevated in SwHi rats. These results provide further insight into the neurobiology of depression and addiction comorbidity and caution that oral and operant psychostimulant self-administration paradigms can yield different, and this case, opposite results.
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Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task.

Filed under: Addiction Rehab

J Psychiatry Neurosci. 2012 Sep 25; 37(6): 110181
Suridjan I, Rusjan P, Addington J, Wilson AA, Houle S, Mizrahi R

Background: The dopamine (DA) D2 receptors exist in 2 states: a high-affinity state (D2 high) that is linked to second messenger systems, responsible for functional effects, exhibits high affinity for agonists (e.g., DA), and a low-affinity state that is functionally inert exhibits lower affinity for agonists. The DA D3 receptor subtype exhibits high agonist affinity, whereas the existence of the multiple affinity states is controversial. Preclinical studies in animal models of psychosis have shown a selective increase of D2 high as the common factor in psychosis, and the D3 receptor has been suggested to be involved in the pathophysiology of schizophrenia. Methods: We studied D2 high and D3 in people at clinical high risk (CHR) for schizophrenia and in antipsychotic-naive patients with schizophrenia using the novel positron emission tomography radiotracer, [11C]-(+)-PHNO. The binding potential nondisplaceable (BPND) was examined in the regions of interest (ROI; caudate, putamen, ventral striatum, globus pallidus, substantia nigra and thalamus) using an ROI and a voxel-wise approach while participants performed a cognitive task. Results: We recruited 12 CHR individuals and 13 antipsychotic-naive patients with schizophreniaspectrum disorder, whom we compared with 12 age- and sex-matched healthy controls. The BPND between patients and controls did not differ in any of the ROIs, consistent with the voxel-wise analysis. Correlations between the BPND in D3-rich regions and psychopathology warrant further investigation. Limitations: In the absence of resting-state (baseline) BPND data, or following a depletion paradigm (i.e., ?-methyl partyrosine), it is not possible to ascertain whether the lack of difference among the groups is owing to different levels of baseline DA or to release during the cognitive task. Conclusion: To our knowledge, the present study represents the first effort to measure the D2 and D3 receptors under a cognitive challenge in individuals putative/prodromal for schizophrenia using [11C]-(+)-PHNO.
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The association between alcohol and tobacco use among elementary and high school students in Crete, Greece.

Filed under: Addiction Rehab

Tob Induc Dis. 2012 Sep 25; 10(1): 15
Tsiligianni I, Vardavas CI, Bouloukaki I, Kosmas E, Verigou E, Kiriakaki M, Siafakas N, Tzanakis N

ABSTRACT: BACKGROUND: Tobacco and alcohol use during adolescence have potential long term health consequences and a possibility of future addiction. METHODS: This cross sectional study took place in 2007 among a convenience sample of 981 adolescents from public elementary and high schools in Eastern Crete, Greece. Following parental consent, an anonymous structured questionnaire including information on personal and family use of alcohol and tobacco was distributed. RESULTS: Among the entire study population, cigarette experimentation was found to be associated with current alcohol use, with an Adjusted Odds Ratio (aOR) of 38.8; (95%C.I: 5.33-58.2) and with having a smoker in the immediate family (aOR 10.3; 95%C.I: 3.14-34.0). Among the subset of elementary school children, cigarette smoking was strongly associated with current alcohol use aOR 9.7; (95%C.I: 2.12-44.3), while the association between smoking experimentation and sibling and parental alcohol use was statistically significant within the entire population (however not among elementary students) with an aOR of 2.76 (95%C.I: 1.24-6.15) and aOR 3.66, (95%C.I: 1.97-6.81) respectively. The elementary child’s gender was not found to be associated with cigarette experimentation among this study population. CONCLUSIONS: Strong associations were found between alcohol use and tobacco experimentation. The potential parental influence on consequent adolescent tobacco and alcohol use was also noted. Potential community based interventions, if launched in Greece, should take the role of the Greek family into account.
HubMed – addiction

 

Gender differences in associations between parental problem drinking and early adolescents’ Internet addiction.

Filed under: Addiction Rehab

J Spec Pediatr Nurs. 2012 Oct; 17(4): 288-300
Jang MH, Ji ES

The purpose was to examine gender differences between parental problem drinking (PPD) and early adolescents’ Internet addiction (IA).This was a cross-sectional, correlational design with 519 (266 boys and 253 girls) early adolescents.PPD had a significant direct effect on IA in boys but not in girls. Significant indirect effects of PPD on IA were evidenced via anxiety-depression and aggression for boys and via family function and aggression for girls.Findings suggest that tailored interventions for the prevention of IA should consider gender.
HubMed – addiction

 

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