GABA(B) receptors and opioid mechanisms involved in homotaurine-induced analgesia.
1. The involvement of GABA(B) receptors and opioid mechanisms in homotaurine-induced analgesia has been investigated in current models of nociception by using a GABA(B) receptor antagonist, morphine, and naloxone. CGP 35348 (50-200 mg/kg IP), a highly selective GABA(B) antagonist, was administered prior to carrying out a dose-response curve of homotaurine (22.6-445 mg/kg IP) antinociceptive effect in the abdominal constriction (mice) and tail flick (rats) tests. 2. The tail flick test was performed in animals pretreated with morphine (0.5 mg/kg SC) and naloxone (1 mg/kg), 15 min before amino acid. Animals treated with saline 10 ml/kg (mice) or 1.25 ml/kg (rats) were included as control for the vehicle used. 3. CGP 35348 antagonized the antinociceptive effect of homotaurine in both tests. The range of doses affected by the interaction depended on the test assayed, but it was coincident for the main part of the dose-response curve. 4. A subanalgesic dose of morphine potentiated the antinociceptive effect of lower doses of homotaurine in the tail flick test. Naloxone pretreatment inhibited the antinociceptive effect of homotaurine. 5. These data imply that GABA(B) receptor subpopulations and opiate mechanisms are involved in the antinociceptive effect of homotaurine. Because functional relationships have been found between GABAergic and opiate systems in analgesic effects, an interaction of the two mechanisms may be operating in the effects described for homotaurine.
Serrano
M I
MI
Department of Pharmacology, Pediatrics and Radiology, University Hospital Virgen Macarena, Seville, Spain.
Serrano
J S
JS
Fernández
A
A
Asadi
I
I
Serrano-Martino
M C
MC
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000701:Analgesics, Opioid; D018755:GABA Agonists; D018080:Receptors, GABA-B; D011957:Receptors, Opioid; D013654:Taurine; C001355:tramiprosate; D009020:Morphine