The GABA agonist THIP, attenuates antinociception in the mouse by modifying central cholinergic transmission.
The effect of THIP, a direct-acting gamma-aminobutyric acid (GABA) receptor agonist, on the antinociceptive response to a variety of agents was examined using the mouse tail-immersion assay. Alone, THIP produced an antinociceptive response in smaller doses (5 mg/kg) but was ineffective at doses exceeding 10 mg/kg. Treatment with THIP (15 mg/kg) was found to block the antinociceptive response to an inhibitor of the uptake of GABA, an inhibitor of GABA-transaminase, a direct-acting GABA receptor agonist and to a cholinesterase inhibitor. In contrast, THIP had no effect on the antinociceptive responses to morphine, clonidine or oxotremorine. The results indicate that large doses of THIP reduce cholinergic activity in a pathway important for mediating the antinociceptive action of GABAergic drugs and physostigmine.
D000344:Afferent Pathways / Q000187:drug effects; D000700:Analgesics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D002799:Cholinergic Fibers / Q000187:drug effects; D018756:GABA Antagonists; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010830:Physostigmine / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects
D000700:Analgesics; D018756:GABA Antagonists; D007555:Isoxazoles; D010080:Oxazoles; D010830:Physostigmine; C015542:gaboxadol