Adolescence versus adulthood: differential effects of drugs of abuse on mesolimbic and nigrostriatal dopamine transmission

Increasing evidence suggests a heightened vulnerability to drugs of abuse in adolescence. During this developmental time frame the brain undergoes extensive remodelling affecting particularly reward system. Such changes involve both mesocortical and mesolimbic pathways. There is evidence for a predominance of ventral striatum (approach system) relative to prefrontal cortex (regulatory system) that produce typical adolescent behaviors (risk-taking, novelty seeking etc.) but, although most of the studies suggest a delayed maturation of the PFC, it is still debated if dopaminergic (DA) transmission in the nucleus accumbens (NAc) of adolescents is hyper- or hypo- responsive. In rodent models, in spite of overwhelming studies on reward function, tested through conditioned place preference or self-administration paradigms, direct evidence on adolescent DA transmission responsiveness to drugs of abuse is limited. The aim of our study was to evaluate differences in mesolimbic DA transmission between adults and adolescent rats and its responsiveness to different drugs of abuse through in vivo microdialysis. Male Sprague-Dawley rats of 5, 6, 7 or 10,11,12 weeks of age were implanted with dual probe, aimed at the shell and core of NAc and challenged with nicotine, Δ9-tetrahydrocannabinol (THC), cocaine, or morphine and extracellular DA levels monitored simultaneously with behaviour. Although no significant differences were observed between adolescents and adults in basal DA levels, neither in the shell nor in the core of NAc, adolescents showed different effects depending on the drug and age of exposure. While no differences were observed in DA transmission responsiveness, both in the shell and in the core of NAc, after cocaine administration, adolescent rats showed greater increase of extracellular DA in the NAc shell following nicotine, THC and morphine compared with adult rats. Moreover behavioral activation was significantly different in adolescent compared with adult rats. While differences observed following THC might be explained by changes occurring in endocannabinoid systems during development, differences following nicotine might be related to differential expression of nicotinic receptors. In conclusion, these results while adding new insight in the development of the reward system during different stages of adolescence provide a likely explanation of the gateway effect of nicotine and THC toward abuse of other illicit substances