A Spontaneous Deletion of ?-Synuclein Is Associated With an Increase in CB1 mRNA Transcript and Receptor Expression in the Hippocampus and Amygdala: Effects on Alcohol Consumption.
A spontaneous deletion of ?-synuclein is associated with an increase in CB1 mRNA transcript and receptor expression in the hippocampus and amygdala: Effects on alcohol consumption.
Filed under: Addiction Rehab
Synapse. 2013 Jan 24;
López-Jiménez A, Walter NA, Giné E, Santos A, Echeverry-Alzate V, Bühler KM, Olmos P, Giezendanner S, Moratalla R, Montoliu L, Buck KJ, López-Moreno JA
?-Synuclein (?-syn) protein and endocannabinoid CB1 receptors are primarily located in presynaptic terminals. An association between ?-syn and CB1 receptors has recently been established in Parkinson’s disease, but it is completely unknown whether there is an association between these two proteins in alcohol addiction. Therefore, we aimed to examine the ?-syn mRNA transcript and protein expression levels in the prefrontal cortex, striatum, amygdala and hippocampus. These brain regions are the most frequently implicated in alcohol and other drug addiction. In these studies, we used C57BL/6 mice carrying a spontaneous deletion of the ?-syn gene (C57BL/6(Snca-/-) ) and their respective controls (C57BL/6(Snca+/+) ). These animals were monitored for spontaneous alcohol consumption (3-10%) and their response to a hypnotic-sedative dose of alcohol (3 g/kg) was also assessed. Compared with the C57BL/6(Snca+/+) mice, we found that the C57BL/6(Snca-/-) mice exhibited a higher expression level of the CB1 mRNA transcript and CB1 receptor in the hippocampus and amygdala. Furthermore, C57BL/6(Snca-/-) mice showed an increase in alcohol consumption when offered a 10% alcohol solution. There was no significant difference in sleep time after the injection of 3 g/kg alcohol. These results are the first to reveal an association between ?-syn and the CB1 receptor in the brain regions that are most frequently implicated in alcohol and other drug addictions. Synapse, 2013. © 2013 Wiley Periodicals, Inc.
HubMed – addiction
Involvement of dynorphin and kappa opioid receptor in yohimbine-induced reinstatement of heroin seeking in rats.
Filed under: Addiction Rehab
Synapse. 2013 Jan 24;
Zhou Y, Leri F, Grella S, Aldrich JV, Kreek MJ
Although kappa opioid receptor (KOP-r) antagonists are known to reduce reinstatement of cocaine, alcohol and nicotine seeking induced by a variety of stressors, the role of KOP-r in yohimbine-induced reinstatement of heroin seeking has not been investigated. Yohimbine, used as a stressor, increases the hypothalamic-pituitary-adrenal (HPA) hormones, causes anxiety and induces heroin craving in humans. The present experiments were undertaken to assess the effects of yohimbine on reinstatement of heroin seeking and associated changes in preprodynorphin (ppDyn) expression and HPA hormonal levels; and to determine whether these effects could be reduced by pretreatment with the selective KOP-r antagonist nor-binaltorphimine (nor-BNI). After heroin self-administration for 12 days (3h/day, 0.05 mg/kg/infusion, i.v.) and extinction for 8 days, reinstatement included the first baseline test after vehicle injection, the second test of yohimbine-induced reinstatement (1.25 mg/kg, i.p.), pretreatment with vehicle or nor-BNI (20 mg/kg, i.p.), the third baseline test after vehicle injection, and the final test of yohimbine-induced reinstatement. Immediately after the last test, several mesolimbic regions and plasma were collected for analyses of ppDyn and KOP-r mRNA levels and HPA hormones. Yohimbine-induced reinstatement was fully blocked by nor-BNI pretreatment. Furthermore, yohimbine elevated plasma HPA hormones, and this increase was blunted by nor-BNI. Finally, rats pre-treated with yohimbine displayed increased ppDyn mRNA levels in the nucleus accumbens shell and central nucleus of the amygdala. These data suggest that the stress responsive ppDyn/KOP-r system is a critical component of the neural circuitry underlying the effect of yohimbine stress on heroin seeking behavior and HPA activity. Synapse, 2013. © 2013 Wiley Periodicals, Inc.
HubMed – addiction
Integrating behavioral economics and behavioral genetics: delayed reward discounting as an endophenotype for addictive disorders.
Filed under: Addiction Rehab
J Exp Anal Behav. 2013 Jan; 99(1): 14-31
Mackillop J
Delayed reward discounting is a behavioral economic index of impulsivity, referring to how much an individual devalues a reward based on its delay in time. As a behavioral process that varies considerably across individuals, delay discounting has been studied extensively as a model for self-control, both in the general population and in clinical samples. There is growing interest in genetic influences on discounting and, in particular, the prospect of discounting as an endophenotype for addictive disorders (i.e., a heritable mechanism partially responsible for conferring genetic risk). This review assembles and critiques the evidence supporting this hypothesis. Via numerous cross-sectional studies and a small number of longitudinal studies, there is considerable evidence that impulsive discounting is associated with addictive behavior and appears to play an etiological role. Moreover, there is increasing evidence from diverse methodologies that impulsive delay discounting is temporally stable, heritable, and that elevated levels are present in nonaffected family members. These findings suggest that impulsive discounting meets the criteria for being considered an endophenotype. In addition, recent findings suggest that genetic variation related to dopamine neurotransmission is significantly associated with variability in discounting preferences. A significant caveat, however, is that the literature is modest in some domains and, in others, not all the findings have been supportive or consistent. In addition, important methodological considerations are necessary in future studies. Taken together, although not definitive, there is accumulating support for the hypothesis of impulsive discounting as an endophenotype for addictive behavior and a need for further systematic investigation.
HubMed – addiction
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