Role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n- propylamino)tetralin in the rat.
The role of 5-HT1A receptors in the antinociceptive action of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was investigated by using the shock titration test in rats. A subcutaneous injection of 300 micrograms/kg 8-OH-DPAT significantly raised the threshold for flinching, jumping and vocalization whereas 100 micrograms/kg only inhibited the flinch response. l-Propranolol and (+)-[N-tert-butyl-3-4-(2-methoxyphenyl)piperazin-1-yl-2-phenyl propanamide dihydrochloride], (+)-WAY100135, two antagonists at 5-HT1A receptors at 10 mg/kg s.c. antagonized the effect of 300 micrograms/kg 8-OH-DPAT on all measures. The effect of 300 micrograms/kg 8-OH-DPAT on the three measures was unmodified in rats which had received 150 micrograms 5,7-dihydroxytryptamine intracerebroventricularly 10 days before testing. The results suggest that 8-OH-DPAT inhibits nociceptive responses by stimulating postsynaptic 5-HT1A receptors.
Cervo
L
L
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Rossi
C
C
Tatarczynska
E
E
Samanin
R
R
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019329:Idazoxan; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D004146:Dioxanes; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C081293:WAY 100135; D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019329:Idazoxan