|Titolo:||Adolescent THC Exposition and vulnerability to drug abuse|
|Data di pubblicazione:||2012|
|Abstract:||Emerging evidence suggests that the use of cannabis during adolescence might lead to neurobiological changes that can affect adult brain functions and behavior. Given the role of endocannabinoid system in this critical phase of life and in the expression of drug reward-related behaviors, the aim of this study was to investigate whether cannabis exposure during adolescence might increase reinforcing effects of abused drugs, such as nicotine, heroin and cannabinoids, in adulthood. For this purpose behavioral, neurochemical studies have been conducted. Male adolescent rats (Sprague-Dawley for nicotine and heroin studies; Lister Hooded for WIN55,212-2 studies) (45 postnatal day, PND) were treated intraperitoneally with increasing doses of THC (2.5, 5 and 10 mg/kg) twice/day for 11 consecutive days. Once animals reached the adulthood (75 PND), we studied the effects of THC exposure on acquisition of nicotine (30 μg/kg/infusion), heroin (30 μg/kg/infusion) and WIN55,212-2 (12,5 μg/kg/infusion) intravenous self-administration behavior using a continuous-reinforcement (fixed-ratio (FR) 1) schedule. Faster acquisition and higher rate of drug intake was considered as index of vulnerability to drug abuse. In a different set of animals that underwent the same drug treatment, dopamine release in the shell of the nucleus accumbens (coordinates from bregma, AP: -1.7, L 0.7, V: -8.2) was measured both in basal condition and after a drug challenge in order to evaluate possible modifications at the level of the mesolimbic dopaminergic system, a brain circuit crucially involved in the mechanisms of reward and dependence related to drug abuse. Behavioral data from nicotine self administration showed no significant difference between the two group of animals although the THC group showed lower, but not significant, responding with respect to the control group. On the other hand, THC exposure increased both heroin and WIN55,212-2 infusions per sessions compared to the control groups. Interestingly, neurochemical data showed a significant difference between two groups of treatment in respect to drug challenge, with a significant lower release of dopamine after nicotine (0.4mg/kg i.p.) and WIN55,212-2 (0.3mg/kg i.v.) and a significant increase after heroin (0.06mg/kg i.v.) in the THC treated animals with respect to control group. Altogether, these results seem to support the hypothesis that early cannabis exposure increased the vulnerability to heroin and cannabinoids abuse in adulthood, with different mechanisms, but not to nicotine abuse|
|Tipologia:||4.1 Contributo in Atti di convegno|
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