“In addition to its role in motor and attentional processes, the subthalamic nucleus (STN) has also been recently demonstrated to be involved in motivational selleck inhibitor function. Indeed, bilateral STN lesions modulate differentially the motivation for natural rewards and drugs of abuse,
increasing motivation for food and decreasing motivation for cocaine in rats. Here, we show that in outbred rats, the STN can modulate the motivation for alcohol according to alcohol preference, without affecting alcohol intake. When performed on ‘HighDrinker’ rats, STN lesions enhanced the breaking point (BP) under a progressive ratio schedule of reinforcement and increased the time spent in the environment previously paired with alcohol access in selleck chemical the place preference paradigm. In contrast, when performed on ‘Low- Drinker’ rats, STN lesions decreased the BP and increased the time spent in the environment paired with water. These results show that STN lesions enhance the motivation for alcohol in rats showing a high alcohol preference, whereas they decrease it in rats showing a low preference for alcohol. These results suggest that the STN plays a complex role in the reward circuit, that is not limited to a dissociation between motivation for natural rewards and drugs of abuse, but takes other factors, such as alcohol
preference, into account.”
“The purpose of this study
was to test the hypothesis that activation of the dynorphin/kappa (kappa)-opioid system has a role in the increased consumption of ethanol in dependent animals. The effects of three opioid receptor antagonists with different effects on opioid Prexasertib receptors, naltrexone, nalmefene, and nor-binaltorphimine (nor-BNI), were compared in their ability to decrease ethanol self-administration in nondependent and ethanol-dependent male Wistar rats. Nalmefene and naltrexone are both opioid receptor ligands with comparable molecular weights and pharmacokinetic profiles, but differing specificity for the three opioid receptor subtypes at low doses, while nor-BNI is a selective kappa-opioid receptor antagonist. Dependence was induced in half the animals by subjecting them to a 4-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14 h per day. Subsequent to dependence induction, nalmefene, naltrexone, and nor-BNI were tested for their ability to modulate self-administration of ethanol in vapor-exposed and control rats. The results indicated that both nalmefene and naltrexone induced a significant dose-dependent decrease in the number of lever presses for ethanol in both groups of animals. However, in ethanol-dependent animals, nalmefene was significantly more effective in suppressing ethanol intake than naltrexone.
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