Addiction biology
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The present study evaluated the involvement of the dorsal hippocampal cannabinoid CB1 receptors in the combined effect of ethanol and nicotine on passive avoidance learning in adult male mice. The results indicated that pre-training administration of ethanol (1 g/kg, i.p.) impaired memory retrieval. Pre-test administration of ethanol (0.5 and 1 g/kg, i.p.) or nicotine (0.5 and 0.7 mg/kg, s.c.) significantly reversed ethanol-induced amnesia, suggesting a functional interaction between ethanol and nicotine. ⋯ The results indicated that AM251 reversed the response of ACPA to the interactive effects of nicotine and ethanol in passive avoidance learning. Furthermore, pre-test intra-CA1 microinjection of the same doses of ACPA or AM251 had no effect on memory retrieval. These findings show that the cannabinoid CB1 receptors of dorsal hippocampus are important in the combined effect of ethanol and nicotine on passive avoidance learning.
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Randomized Controlled Trial
Effects of the NK1 antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers.
Pre-clinical studies suggest that the neurokinin-1 (NK1) receptor may modulate the response to opioids, with NK(1) inactivation leading to decreased opioid reinforcement, tolerance and withdrawal. Aprepitant is a selective NK1 antagonist currently marketed for clinical use as an anti-emetic. This 6-week in-patient study used a randomized, double-blind, double-dummy, within-subject, crossover design. ⋯ Some objective measures (respiratory function, observer-rated opioid agonist effects) were similarly enhanced by pre-treatment with the highest dose of aprepitant. All dose combinations were safely tolerated. These findings are discussed in the context of the potential utility of NK1 antagonists in the treatment of opioid use disorders.
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Cannabidiol is a non-psychotomimetic constituent of Cannabis sativa, which induces central effects in rodents. It has been shown that cannabidiol attenuates cue-induced reinstatement of heroin seeking. However, to the best of our knowledge, its effects on brain stimulation reward and the reward-facilitating effects of drugs of abuse have not yet been examined. ⋯ The present findings indicate that cannabidiol does not exhibit reinforcing properties in the ICSS paradigm at any of the doses tested, while it decreases the reward-facilitating effects of morphine. These effects were mediated by activation of 5-HT1A receptors in the dorsal raphe. Our results suggest that cannabidiol interferes with brain reward mechanisms responsible for the expression of the acute reinforcing properties of opioids, thus indicating that cannabidiol may be clinically useful in attenuating the rewarding effects of opioids.
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Social/peer influences are among the strongest predictors of adolescent drug use. However, this important subject does not get much attention in pre-clinical studies. We recently observed that exposure to different social partners modulates morphine locomotor sensitization. ⋯ Additionally, 40 mg/kg morphine was sufficient to establish morphine CPP in the saline cage-mate animals. These results indicate that social environment has an effect on the rewarding properties of morphine. It suggests that exposure to different peers can alter the abuse potential of opioids and potentially other illicit drugs.