Potentiation of kappa-opioid receptor agonist-induced analgesia and hypothermia by fluoxetine.
The effect of fluoxetine, a selective 5-HT reuptake inhibitor on the analgesic and hypothermic response of trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methane sulphonate (U-50,488H) and (+/-)-trans-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzo[b] thiophene-4-acetamide (PD 117302), kappa-opioid receptor agonists, was determined in female Sprague-Dawley rats using the tail-flick method and telethermometer, respectively. Intraperitoneal injections of U-50,488H (U50) and PD 117302 (PD117) produced a dose-dependent analgesic and hypothermic response. Fluoxetine (10 mg/kg, i.p.) by itself did not produce an analgesic response. The analgesic response to U50 (10, 20, and 40 mg/kg, i.p.) and PD117 (7.5, 15, and 22.5 mg/kg, i.p.) was potentiated by fluoxetine injected intraperitoneally 60 min prior to the injection of kappa-opioid agonists. Similarly, the hypothermic response of U50 (20 and 40 mg/kg, i.p.) and PD117 (7.5, 15, and 22.5 mg/kg, i.p.) was potentiated by fluoxetine. The results indicate that selective kappa-opioid receptor agonists-induced analgesia and hypothermia is potentiated by fluoxetine, suggesting the role of extracellular 5-HT in the kappa-opioid receptor-mediated analgesia and hypothermia.
Nemmani
K V
KV
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Phase-X, S.A.S., 160 062 (Pb), Nagar, India.
Gullapalli
S
S
Ramarao
P
P
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000698:Analgesia; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012701:Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000701:Analgesics, Opioid; D000927:Anticonvulsants; D005473:Fluoxetine; D011758:Pyrroles; D017473:Receptors, Opioid, kappa; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes; C054718:PD 117302