5-HT2 receptors differentially modulate dopamine-mediated auto-inhibition in A9 and A10 midbrain areas of the rat

5-HT (20 microM) enhanced dopamine (DA) D2-like receptor mediated reduction of the firing rate of DA neurons in the substantia nigra pars compacta (A9) and ventral tegmental area (A10) in a rat midbrain slice preparation. Quinpirole (30 nM) induced a mean reduction of the firing rate in A9 and A10 DA neurons to 64 +/- 4%, respectively, 71 +/- 5% of the baseline value. Bath application of 5-HT in the presence of quinpirole further reduced the firing rate to 37 +/- 7% in A9 and 33 +/- 13% in A10. The 5-HT2 receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, 500 nM) enhanced quinpirole-induced reduction of firing rate of A10 DA neurons, but not of A9 DA neurons, suggesting that different 5-HT receptor subtypes are involved in modulation of dopamine D2-like receptor mediated inhibition in the two regions. The selective 5-HT2A receptor antagonist MDL100907 and the selective 5-HT2C receptor antagonist SB242084 (50 and 500 nM) both abolished the enhancement of quinpirole-induced reduction by either 5-HT or DOI, suggesting the involvement of direct and indirect (possibly via interneurons) modulation pathways in A10. The involvement of 5-HT and specific 5-HT2 receptors in augmentation of auto-inhibition in A10 could have important implications for our understanding of the mechanism of atypical antipsychotic drug action.