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.
Seth
P
P
Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, Jadavpur, Calcutta, India.
Gajendiran
M
M
Ganguly
D K
DK
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011433:Propranolol