Role of the medial prefrontal cortex in 5-HT(1A) receptor-induced inhibition of 5-HT neuronal activity in the rat

Abstract

1. We examined the involvement of the frontal cortex in the 5-HT(1A) receptor-induced inhibition of 5-HT neurones in the dorsal raphe nucleus (DRN) of the anaesthetized rat using single-unit recordings complemented by Fos-immunocytochemistry. 2. Both transection of the frontal cortex as well as ablation of the medial region of the prefrontal cortex (mPFC) significantly attenuated the inhibition of 5-HT neurones induced by systemic administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT (0.5-16 μg kg-1, i.v.). In comparison, the response to 8-OH-DPAT was not altered by ablation of the parietal cortex. The inhibitory effect of 8-OH-DPAT was reversed by the 5-HT(1A) receptor antagonist, WAY 100635 (0.1 mg kg-1, i.v.) in all neurones tested. 3. In contrast, cortical transection did not alter the sensitivity of 5-HT neurones to iontophoretic application of 8-OH-DPAT into the DRN. Similarly, cortical transection did not alter the sensitivity of 5-HT neurones to systemic administration of the selective 5-HT reuptake inhibitor, paroxetine (0.1-0.8 mg kg-1, i.v.). 4. 8-OH-DPAT evoked excitation of mPFC neurones at doses (0.5-32 μg kg-1, i.v.) in the range of those which inhibited 5-HT cell firing. At higher doses (32-512 μg kg-1, i.v.) 8-OH-DPAT inhibited mPFC neurones. 8-OH-DPAT (0.1 mg kg-1, s.c. also induced Fos expression in the mPFC. The neuronal excitation and inhibition, as well as the Fos expression, were antagonized by WAY 100635. 5. These data add further support to the view that the inhibitory effect of 5-HT(1A) receptor agonists on the firing activity of DRN 5-HT neurones involves, in part, activation of a 5-HT(1A) receptor-mediated postsynaptic feedback loop centred on the mPFC.