Desensitization of spinal 5-HT1A receptors to 8-OH-DPAT: an in vivo spinal reflex study

Serotonergic influence on spinal monosynaptic transmission and the desensitization of spinal 5-HT1A receptors following a single pretreatment with a 5-HT1A ligand were examined in vivo in acutely spinalized adult rats. Administration of a selective 5-HT1A agonist, 8-OH-DPAT (0.1 mg kg-1) significantly depressed the monosynaptic mass reflex (MMR) amplitude, which was prevented effectively by S(-)-propranolol, a 5-HT1A antagonist. The inhibitory effect of 8-OH-DPAT on MMR amplitude was significantly attenuated with a single dose of 8-OH-DPAT (1 mg kg-1, s.c.) administered 24 h before the experiments, indicating a marked desensitization of spinal 5-HT1A receptors. Desensitization of 5-HT1A receptors could be reversed by treatment of spiperone (1 mg kg-1, i.p.) 3 h before 8-OH-DPAT pretreatment. These results demonstrate that 5-HT1A receptor functionally modulates the spinal motor output and confirms the ability of 8-OH-DPAT to desensitize presynaptic 5-HT1A receptors as observed for the first time in rat spinal cord.