Increasing evidences suggest 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 transmission in the nucleus accumbens (NAc) of adolescents is hyper- or hypo- reactive. In rodent models, in spite of overwhelming studies on reward function, tested through conditioned place preference or self-administration paradigms, direct evidences on adolescent dopamine (DA) transmission responsiveness to drugs of abuse are limited. The aim of our study was to evaluate if there are differences in mesolimbic DA transmission between adults and adolescents after administration of 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 (0.4 mg/kg s.c.), Δ9-tetrahydrocannabinol (THC, 1.0 mg/kg i.p.), cocaine (10 mg/kg i.p.) or morphine (1.0 mg/kg s.c.) 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 and core of NAc, adolescents showed different effects depending on the drug and on the age of exposure. While no differences were observed in DA transmission responsiveness, both in the shell and in the core of NAc, after morphine or nicotine administration, rats at 6 weeks of age showed greater increase of DA levels in the NAc shell following 1.0 mg/kg i.p. of THC compared to adult rats. Moreover 5 weeks animals appear to be less sensitive to the DA increasing effects of cocaine (10 mg/kg i.p.) compared to adolescents of 6 and 7 weeks and to adults. While differences observed following THC and cocaine challenge might be explained respectively by changes occurring in endocannabinoid system during development and in DA uptake transporter (DAT) levels as reported by previous studies, these results add new insights in the development of the reward system during different stages of adolescence.
Adolescence versus adulthood: differential effects of drugs of abuse on mesolimbic dopamine transmission
CORONGIU, SILVIA;DESSI', CHRISTIAN;
2015-01-01
Abstract
Increasing evidences suggest 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 transmission in the nucleus accumbens (NAc) of adolescents is hyper- or hypo- reactive. In rodent models, in spite of overwhelming studies on reward function, tested through conditioned place preference or self-administration paradigms, direct evidences on adolescent dopamine (DA) transmission responsiveness to drugs of abuse are limited. The aim of our study was to evaluate if there are differences in mesolimbic DA transmission between adults and adolescents after administration of 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 (0.4 mg/kg s.c.), Δ9-tetrahydrocannabinol (THC, 1.0 mg/kg i.p.), cocaine (10 mg/kg i.p.) or morphine (1.0 mg/kg s.c.) 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 and core of NAc, adolescents showed different effects depending on the drug and on the age of exposure. While no differences were observed in DA transmission responsiveness, both in the shell and in the core of NAc, after morphine or nicotine administration, rats at 6 weeks of age showed greater increase of DA levels in the NAc shell following 1.0 mg/kg i.p. of THC compared to adult rats. Moreover 5 weeks animals appear to be less sensitive to the DA increasing effects of cocaine (10 mg/kg i.p.) compared to adolescents of 6 and 7 weeks and to adults. While differences observed following THC and cocaine challenge might be explained respectively by changes occurring in endocannabinoid system during development and in DA uptake transporter (DAT) levels as reported by previous studies, these results add new insights in the development of the reward system during different stages of adolescence.
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