Treating neonatal rats with 6-hydroxydopamine induced an increase in voluntary alcohol consumption

Brain dopamine (DA) and serotonin (5-HT) neurotransmission have been implicated in the mediation of alcohol-seeking behavior. We examined the effects of treatment of neonatal rats (3 days after birth) with the neurotoxin 6-hydroxydopamine (6-OHDA; 100 microg/10 microl, intracerebroventricularly) on the relationship between the levels of neurotransmitters and alcohol drinking behavior at the age of 14 weeks. 6-OHDA treatment reduced the levels of DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens (ACC), frontal cortex, striatum (STR), tegmentum/substantia nigra, and dorsal raphe nucleus. 5-HT levels in the ACC and STR were increased in the 6-OHDA-treated rats. 6-OHDA-treated rats showed increased alcohol consumption. There was a significant change in the ratio of [5-hydroxyindoleacetic acid]/[5-HT] in the ACC and STR of the treated rats, but no difference in the ratio of [DOPAC]/[DA] between the sham-operated controls and treated rats. 6-OHDA-treated rats had dopaminergic dysfunction in the five brain regions related to the reward system, in part, and a decrease in 5-HT turnover, including the accumulation of 5-HT in the ACC and STR. Furthermore, basal extracellular releases of DA and 5-HT of the ACC were significantly lower in the 6-OHDA-treated rats, compared with the controls. It was suggested that alcohol seeking behavior is associated with the alterations of dopaminergic neurons and the release of 5-HT in the mesocorticolimbic system.