SEROTONIN POTENTIATES DOPAMINE-INHIBITION OF VENTRAL TEGMENTAL AREA NEURONS IN-VITRO

1. The ventral tegmental area (VTA) has been implicated in both the re warding effects of drugs of abuse and the etiology of schizophrenia. W e report here that serotonin (5-HT) potentiates the inhibitory effect of dopamine on dopaminergic VTA neurons. Dopamine (0.5-10 mu M) inhibi ted the spontaneous firing of putative dopamine-containing neurons of the VTA. 5-HT (5-10 mu M) itself did not significantly alter the spont aneous firing rate; however, in the presence of 5-HT, the inhibitory p otency of dopamine was significantly increased. 2. The inhibitory pote ncy of the dopamine agonist quinpirole was also increased by 5-HT. 3. 5-HT-induced potentiation was also produced by the selective 5-HT2 ago nist (+/-)-2,5-dimethoxy-4-iodoamphetamine, and was reversed by the se lective 5-HT2 antagonist ketanserin. 4. This novel action of 5-HT on d opaminergic neurons has important implications for the development of drugs to treat schizophrenia, and for the identification of agents tha t will be useful in treating drug abuse disorders like alcoholism.