Opioid and prostaglandin mechanisms involved in the effects of GABAergic drugs on body temperature.
1. Intraperitoneal (i.p.) injection to restrained rats of GABA (250-1000 mg/kg) or the GABAA-receptor agonist muscimol (0.05-1 mg/kg) induced a dose-dependent decrease in body temperature (BT). 2. Intraperitoneal injection of low doses of the GABAB-receptor agonist (+/-)-baclofen (1-10 mg/kg) did not significantly affect BT. However, baclofen, at high doses (30 mg/kg), produced an increase in BT. 3. Pretreatment with either bicuculline (3 mg/kg) or naloxone (1 mg/kg) did not significantly modify the hypothermic response observed with GABA or muscimol, except for the high dose of GABA (1000 mg/kg) which was potentiated by bicuculline pretreatment. 4. Indomethacin pretreatment (5 mg/kg) significantly antagonized the hypothermia induced by GABA and muscimol. 5. Injection of baclofen alone (1 mg/kg) did not significantly affect BT, but in presence of the GABAA antagonist bicuculline, baclofen significantly decreased BT. 6. Baclofen-induced hyperthermia appear to be via prostaglandin and opioid mechanisms since both indomethacin and naloxone abolish this effect. 7. The hypothermia induced by GABA-agonists appears to be due to simultaneous activation of GABAA and GABAB receptors, while the hyperthermic effect of baclofen appears to be due to stimulation of GABAB receptors. 8. The present results suggest that involvement of prostaglandins in the effects of GABA, muscimol and baclofen, while endogenous opiates seem to be implicated only in baclofen induced hyperthermia. 9. It can be concluded that GABA may be involved in the control of BT through GABAA and GABAB receptors.
Sancibrian
M
M
Departamento de Farmacologia, Pediatria y Radiologia, Facultad de Medicina, Universidad de Sevilla, Spain.
Serrano
J S
JS
Miñano
F J
FJ
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D009118:Muscimol / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*
D004723:Endorphins; D011453:Prostaglandins; D011963:Receptors, GABA-A; D009118:Muscimol; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D007213:Indomethacin; D001640:Bicuculline