Supersensitivity to the antinociceptive effect of a 5-HT1 receptor agonist after lesion of raphe-spinal serotonergic neurones.
The actions of the 5-hydroxytryptamine type-1B (5-HT1) receptor agonist 1(m-chlorophenyl)piperazine (mCPP) on response latencies in the tail-flick test and tail skin temperature were examined in mice after pretreatment with the 5-HT neurotoxin, 5,6-dihydroxytryptamine (5,6-DHT). All the compounds were given intrathecally. The level of 5-HT in spinal cord was reduced by 79% 4 days after intrathecal injection of 5,6-DHT (10 micrograms). There was a significant relationship between the tail-flick latency and tail skin temperature, and the reduced baseline tail-flick latencies induced by 5,6-DHT were non-significant after the change in skin temperature was taken into account. Intrathecal mCPP (5 micrograms) significantly increased the tail-flick latency and significantly reduced the tail skin temperature in 5,6-DHT pretreated animals when compared to control animals. These differences in tail-flick latencies could not be explained by alterations in skin temperature. The results provide evidence that neurotoxic lesion of descending 5-HT pathways induces supersensitivity to the antinociceptive effect of 5-HT1 receptor stimulation.
Eide
P K
PK
Department of Physiology, University of Bergen, Norway.
Hole
K
K
Broch
O J
OJ
D015115:5,6-Dihydroxytryptamine; D000818:Animals; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012881:Skin Temperature; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013563:Sympathectomy, Chemical
D010879:Piperazines; D011985:Receptors, Serotonin; D012701:Serotonin; C015068:1-(3-chlorophenyl)piperazine; D015115:5,6-Dihydroxytryptamine