5-HT sub(2) receptors differentially modulate dopamine-mediated auto-inhibition in A9 and A10 midbrain areas of the rat

• Published in: Neuropharmacology Vol. 46; no. 4; pp. 504 - 510
• Main Authors: Olijslagers, JE, Werkman, T R, McCreary, A C, Siarey, R, Kruse, C G, Wadman, W J
• Format: Journal Article
• Language: English
• Published: 01-03-2004
• ISSN: 0028-3908
• DOI: 10.1016/j.neuropharm.2003.10.003

5-HT (20 mu M) enhanced dopamine (DA) D sub(2)-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-HT sub(2) 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 D sub(2)-like receptor mediated inhibition in the two regions. The selective 5-HT sub(2A) receptor antagonist MDL100907 and the selective 5-HT sub(2C) 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-HT sub(2) receptors in augmentation of auto-inhibition in A10 could have important implications for our understanding of the mechanism of atypical antipsychotic drug action.