Nicotine withdrawal produces a decrease in extracellular levels of dopamine in the nucleus accumbens that is lower in adolescent versus adult male rats

The behavioral effects of nicotine withdrawal are lower in adolescent versus adult rats. However, the neurochemical mechanisms that mediate these developmental differences are unknown. Previous studies have shown that extracellular levels of dopamine in the nucleus accumbens (NAcc) are reduced in adult rats experiencing withdrawal. This study compared dopamine levels in the NAcc of male adolescent and adult rats experiencing nicotine withdrawal. Animals were prepared with subcutaneous pumps that delivered an equivalent nicotine dose in these age groups. Following 13 days of nicotine exposure, rats were implanted unilaterally with microdialysis probes into the NAcc and ipsilateral ventral tegmental area (VTA). The next day, dialysate levels were collected following systemic administration of the nicotinic-receptor antagonist mecamylamine to precipitate withdrawal. Mecamylamine produced an average % decrease in NAcc dopamine that was lower in adolescents (20%) versus adults (44%). Similar developmental differences were observed with the dopaminergic (DOPAC and HVA) but not serotonergic (5-HIAA) metabolites. A follow-up study compared NAcc dopamine in adolescent and adult rats receiving intra-VTA administration of bicuculline, which reduces gamma-aminobutyric acid (GABA) inhibition of dopamine transmission. The results revealed that blockade of GABA(A) receptors in the VTA produced a two-fold increase in NAcc dopamine of adults but not adolescents. These results provide a potential mechanism involving dopamine that mediates developmental differences in nicotine withdrawal. Specifically, they suggest that GABA systems are underdeveloped during adolescence and this reduced inhibition of dopamine neurons in the VTA may lead to reduced decreases in NAcc dopamine of young animals experiencing withdrawal.