RESUMEN
Adolescence is a crucial developmental period where neural circuits are refined and the brain is especially vulnerable to external insults. The endocannabinoid (eCB) system undergoes changes during adolescence which affect the way in which it modulates the development of other systems, in particular dopamine circuits, which show protracted development into adolescence. Given the rise of cannabis use by adolescents and young people, as well as variants containing increasingly higher concentrations of THC, it is now crucial to understand the unique effects of adolescent exposure to cannabis on the developing brain and it might shape future adult vulnerabilities to conditions such as psychosis, schizophrenia, addiction and more. Here we discuss the development of the eCB system across the lifespan, how CB1 receptors modulate dopamine release and potential neurobiological and behavioral effects of adolescent THC exposure on the developing brain such as alterations in excitatory/inhibitory balance during this developmental period.
Asunto(s)
Encéfalo , Cannabis , Adolescente , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Encéfalo/fisiopatología , Cannabis/toxicidad , HumanosRESUMEN
BACKGROUND: Previous research has found that rats behaviorally screened for high (vs. low) wheel running were more vulnerable to cocaine abuse. To assess the extent to which a genetic component is involved in this drug-abuse vulnerability, rats selectively bred for high or low voluntary running (HVR or LVR, respectively) were examined for differences in cocaine seeking in the present study. METHODS: Female rats were trained to lever press for food and then were assessed for differences in acquisition of cocaine (0.4mg/kg; i.v.) self-administration across 10 sessions. Once acquired, rats self-administered cocaine for a 14-day maintenance phase, followed by a 14-day extinction phase when cocaine was no longer available. Subsequently, reinstatement of cocaine seeking was examined with priming injections of cocaine (5, 10 & 15mg/kg), caffeine (30mg/kg), yohimbine (2.5mg/kg) and cocaine-paired cues. RESULTS: A greater percentage of LVR rats met the acquisition criteria for cocaine self-administration and in fewer sessions than HVR rats. No differences in responding for cocaine were observed between phenotypes during maintenance. However, during extinction LVR rats initially responded at higher rates and persisted in cocaine seeking for a greater number of sessions. No phenotype differences were observed following drug and cue-primed reinstatement of cocaine seeking. CONCLUSIONS: In general, LVR rats were more sensitive to the reinforcing effects of cocaine than HVR rats during periods of transition into and out of cocaine self-administration. Thus, LVR rats sometimes showed a greater vulnerability cocaine seeking than HVR rats.