Baclofen and antidepressant--induced antinociception in formalin test: possible GABA(B) mechanism involvement.
In this study, the influences of GABA(B) agents on antidepressant-induced antinociception in the mouse formalin test have been investigated. The GABA(B) receptor agonist baclofen (2.5, 5 and 10 mg/kg) induced a dose-dependent antinociception in the second phase of the formalin test. This response was inhibited by the GABA(B) receptor antagonist, CGP35348 [P-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid], in a dose-dependent manner. The antagonist by itself also induced antinociception. Single administration of the antidepressants citalopram (10, 20, 40 and 80 mg/kg), desipramine (20, 40, 80 mg/kg) or imipramine (10, 20 and 40 mg/kg) also induced antinociception in both phases of the formalin test. CGP35348 (100 and 200 mg/kg) pretreatment reduced the response induced by the tricyclic antidepressants. A combination of baclofen with the tricyclic antidepressant did not potentiate antinociception induced by antidepressants, but a decrease in the response induced by higher dose of baclofen was shown. It is concluded that GABA mechanism(s) may modulate the antidepressant-induced antinociception.
Sabetkasai
M
M
Department of Pharmacology, School of Medicine, Shaheed-Beheshti University of Medical Science, Tehran, Iran.
Khansefid
N
N
Yahyavi
S H
SH
Zarrindast
M R
MR
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001418:Baclofen / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000502:physiology*
D018712:Analgesics, Non-Narcotic; D000928:Antidepressive Agents; D018755:GABA Agonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C066430:CGP 35348; D001418:Baclofen