Prefrontal levels of 5-HIAA, but not dopamine, predict alcohol consumption in male wistar rats following 6-OHDA lesions

Abstract To examine the effects of dopamine (DA) on alcohol consumption, male Wistar rats were subjected iether to 6-OHDA lesions of the frontal cortex (MPFC) or to a sham lesion/no lesion. Following surgery, rats were trained to drink alcohol on a sucrose-fading paradigm over the course of 6 weeks, at the completion of which they consumed a solution of 3% sucrose/10% alcohol. Daily consumption of alcohol was computed for each rat. Animals were sacrificed and the MPFC, nucleus accumbens (NA), and ventral tegmentum (VTA) were removed. Levels of DA and its metabolites (i.e., HVA and DOPAC), norepinephrine (NE), and serotonin (5-HT) and its metabolite (i.e., 5-HIAA) were measured for each brain region using HPLC with electrochemical detection. Post hoc analyses were run examining the relationship of DA and its metabolites, 5-HT and its metabolite (5-HIAA), and norepinephrine (NE) in the MPFC, NA, and VTA with alcohol consumption. The 6-OHDA lesions depleted DA to 74.5% of control levels in the MPFC, but did not significantly affect alcohol consumption. Post hoc analyses found that the “high” alcohol consumption group had significantly reduced levels of MPFC 5-HIAA in comparison to the “low” consumption group, but that there was no relationship of 5-HIAA levels in the VTA or NA to alcohol consumption. These findings suggest that MPFC DA is not critically involved in the regulation of alcohol consumption. They further suggest that MPFC serotonergic systems may play an important role in the regulation of alcohol consumption, although future experimentation directly manipulating 5-HT systems in the MPFC will be required to fully assess these findings.