Serotonin microinfusion into the ventral tegmental area increases accumbens dopamine release

Abstract

The effects of microinfusion of serotonin (5-HT) agents as well as glutamate and muscimol into the ventral tegmental area (VTA) on dopamine (DA) release in the ipsilateral nucleus accumbens (ACC) were investigated in freely moving rats, using a push-pull perfusion procedure. The baseline values for DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were approximately 0.24, 8.4, 2.1 and 2.7 pmol/15 min, respectively, in the push-pull perfusate of the ACC. When microinfused into the VTA, glutamate (0.74 μg) significantly ( p<0.05) increased the contents of DOPAC (110%) and HVA (90%) over baseline levels in the perfusate. On the other hand, 0.5 μg muscimol (a γ-amino- n-butyric acid, GABA, agonist) significantly, ( p<0.05) decreased both DA (40%) and DOPAC (20%) levels relative to baseline values. Administration of 2 μg 5-HT into the VTA caused a significant ( p<0.05) elevation in the perfusate levels of DOPAC (80%) and HVA (70%) over baseline values. A similar effect was obtained with a nonselective 5-HT 1 agonist but not with a selective 5-HT 1A agonist. The results suggest that 5-HT innervations in the VTA may have an excitatory action possibly via 5-HT 1B rather than 5-HT 1A receptors on the mesolimbic DA system projecting to the ACC and that this DA system may also be regulated by glutamatergic and GABAergic (via GABA A receptors) inputs.