Harman-induced changes of extracellular concentrations of neurotransmitters in the nucleus accumbens of rats

Several beta-carbolines, including harman, induce voluntary ethanol intake in rats. It is not clear yet which mechanisms cause these effects. One possibility is the stimulation of the mesolimbic reward system. In vivo microdialysis was used to investigate the effects of acute injections of harman (1-methyl-beta-carboline) on extraneuronal concentrations of dopamine and 5-hydroxytryptamine in the nucleus accumbens, which is part of the mesolimbic reward system. Administration of harman (2.27 mu mol/kg, intraperitoneal application) elicited an increase of the dopamine efflux by 72% which returned to basal levels after approximately 300 min. In contrast, administration of an intermediate dose of harman (13.65 mu mol/kg, intraperitoneal application) caused a significant decrease in efflux, to 76% of basal levels. Still higher doses induced again an increased extracellular dopamine concentration. This change was statistically significant in only a subgroup of rats, possibly because individual animals reacted differently to the high doses. Extracellular 5-hydroxytryptamine in the nucleus accumbens was increased during the first 2 h after the administration of high doses (40.94 and 81.93 mu mol/kg, intraperitoneal application). These findings indicate that harman affects the activity of mesolimbic dopaminergic neurons following a U-shaped dose-response relationship.