Mechanisms of effects of intrathecal serotonin on nociception and blood pressure in rats.
The effects of intrathecal (i.t.) serotonin (5-HT) and a number of serotonergic receptor agonists on nociception and blood pressure were examined in rats. Intrathecal 5-HT produced dose-dependent inhibition of the nociceptive tail-flick reflex (ED50 = 100.0 micrograms) and dose-dependent depressor effects. The 5-HT1A agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin and the 5HT1B agonist 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969) also produced depressor effects but, in contrast to 5-HT, facilitated the tail-flick reflex, whereas the 5-HT2 agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212) and quipazine produced dose-dependent antinociception and had little or no effect on blood pressure. These results suggest that the antinociceptive and depressor effects of i.t. 5-HT are mediated by spinal 5-HT2 and 5-HT1 receptors, respectively. In other experiments, rats chronically treated with i.t. 5-HT developed tolerance to its antinociceptive effects, whereas chronic i.t. morphine or clonidine did not produce cross-tolerance to i.t. 5-HT. These results suggest that serotonergic spinal antinociceptive mechanisms are distinct from the mechanisms by which opioid receptor and alpha-2 adrenoceptor agonists produce antinociception in the spinal cord.
Solomon
R E
RE
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City.
Gebhart
G F
GF
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000698:Analgesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D013373:Substance P; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin