Participation of GABAergic systems in the production of antinociception by various stresses in mice.
Based on the data that diazepam, a benzodiazepine (BZP) receptor agonist, antagonized psychological (PSY)-stress induced analgesia (SIA) without prominent action on footshock (FS)- and forced swimming (SW)-SIA and that BZP receptors are coupled with GABA receptors, we examined how the GABAergic system participates in the production of various SIAs. Muscimol, a GABAA receptor agonist, at doses of 0.25 to 1.0 mg/kg, affected each SIA differently, suppressed PSY-SIA at 0.25 mg/kg but tended to potentiate it at 1.0 mg/kg, potentiated SW-SIA dose-dependently and did not affect FS-SIA at the doses employed. Both bicuculline, a GABAA receptor antagonist, 0.5 to 2.0 mg/kg, and picrotoxin, a Cl- channel blocker, 0.25 to 1.0 mg/kg, dose-dependently suppressed PSY- and FS-SIA. Meanwhile, the effects of both drugs on SW-SIA were less than those on PSY- and FS-SIA, namely, bicuculline slightly inhibited it only at 2.0 mg/kg, and picrotoxin did not produce any appreciable effect even at the highest dose. Baclofen, a GABAB receptor agonist, at 5.0 and 10.0 mg/kg had no influence on each SIA. On the contrary, CGP 35348, a GABAB receptor antagonist at 20 to 100 mg/kg caused the dose-dependent blockade of FS-SIA, but affected neither PSY- nor SW-SIA. The production of PSY- and SW-SIA is attributable to the GABAA receptors/Cl- channel mediated mechanism alone, while that of FS-SIA involves both GABAA and GABAB receptor mediated systems. Thus, GABAergic systems play an important role in the production of each SIA; however, the participation of the receptor subtypes in the mechanism was different from each other.
Tokuyama
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Takahashi
M
M
Kaneto
H
H
D000698:Analgesia; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D058787:GABA-A Receptor Antagonists; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009118:Muscimol / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology; D013315:Stress, Psychological / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001418:Baclofen; D001640:Bicuculline; D058787:GABA-A Receptor Antagonists; D009118:Muscimol; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348