Repeated ethanol exposure during adolescence alters the developmental trajectory of dopaminergic output from the nucleus accumbens septi

Individuals who begin using alcohol prior to 14 years of age are 4 times more likely to progress to addiction than those who do not initiate use until 21 years of age. The nucleus accumbens septi undergoes dramatic developmental transitions during the adolescent period, and dopaminergic activity within this region has been identified as a central neurochemical mediator of drug reward, addiction and dependence. Thus, alcohol-induced neurochemical alterations in dopaminergic activity within this brain region likely mediate the heightened vulnerability to addiction observed in adolescent alcohol users. To investigate this idea, Sprague–Dawley rats were exposed to intraperitoneal injections of either saline or ethanol (0.5, 1.0 or 2.0 g/kg) twice daily over four days beginning on postnatal day 21, 31, 41 or 56. Cannulas were implanted toward the nucleus accumbens septi, subsequent in vivo microdialysis was used to collect samples, and both basal and ethanol-stimulated dopamine overflow was measured using high performance liquid chromatography with electrochemical detection. A developmental transition in basal levels of dopamine in the nucleus accumbens septi was apparent with peak levels at postnatal day 45. An ethanol challenge produced unique responses across ages, with greater peak effects relative to baseline in younger animals (postnatal day 25 and 35). Following repeated exposure to ethanol, a significant increase in basal dopamine was apparent for all ages, and when these animals were challenged with ethanol, peak effects relative to baseline were decreased in younger animals, but unchanged in older animals (postnatal day 45 and 60). Results indicate that there is a key developmental transition in the ability of rats to adapt to the effects of repeated ethanol exposure, which occurs between postnatal day 35 and 45. This alteration may explain the increased addiction vulnerability observed in individuals who initiate alcohol use during early adolescence.