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Role of cholinergic and GABAergic systems in the feedback inhibition of dorsal raphe 5-HT neurons

Haddjeri, Nasser1; Lucas, Guillaume2; Blier, Pierre1,3

Synaptic Transmission

Several observations indicate that 5-HT1A receptors found on a long neuronal feedback loop, originating from the medial prefrontal cortex, regulate 5-HT neuronal firing. In the present study, the muscarinic (M) receptor antagonists atropine and scopolamine as well as the M2 receptor antagonist AF-DX 116, but not the preferential M1 receptor antagonist pirenzepine, reduced the suppressant effect of the 5-HT1A receptor agonist 8-OH-DPAT on the spontaneous firing activity of rat dorsal raphe 5-HT neurons. Moreover, AF-64A-induced lesions of cholinergic neurons directly in the medial prefrontal cortex and after its i.c.v. injection attenuated the effect of 8-OH-DPAT. Finally, the NMDA receptor antagonist (+) MK-801 and the GABAB receptor antagonist SCH-50911, but not the GABAA receptor antagonist (−) bicuculline, dampened the latter response. The present study unveiled a key role for the cholinergic and GABAergic systems in the feedback inhibition of dorsal raphe 5-HT neurons.

1Department of Psychiatry, Brain Institute, University of Florida P.O. Box 100256, Gainesville, Florida, USA 32610-0256

2Neurobiological Psychiatry Unit, McGill University, 1033 Pine Avenue West, Montréal, Québec, Canada H3A 1A1

3Corresponding Author: Pierre Blier

Acknowledgements: This work was supported in part by the Medical Research Council of Canada (MRC) grant (MT-11014 to P.B), N.H. is in receipt of a Fellowship from the MRC of Canada (MFE-40177), G.L. of a Fellowship of the Royal Victoria Hospital Institute and P.B. of salary support from the University of Florida.

Received 9 August 2000; accepted 16 August 2000

© 2000 Lippincott Williams & Wilkins, Inc.