Potential interactions between GABAb and cholinergic systems: baclofen augments scopolamine-induced performance deficits in the eight-arm radial maze.
Sixteen male Fischer-344N rats were trained on a eight-arm radial maze task for food reinforcement. The effects of various doses of baclofen (1.25 or 2.50 mg/kg) and scopolamine (0.188, 0.375, and 0.750 mg/kg) were determined alone and in combination. Relative to vehicle controls, baclofen alone did not affect performance in the radial arm maze (number correct in the first eight responses, total errors) or the time required to complete the maze. Scopolamine alone decreased the number of correct responses in the first eight arm choices, while increasing both the number of errors and the time necessary to complete the maze. When the two drugs were co-administered, baclofen had no effect on the number of errors or time required to complete the maze in the presence of scopolamine; however, in combination with the high dose of scopolamine, it significantly increased the number of errors made during the first eight choices. Baclofen thus can exacerbate some radial arm maze dificits produced by an anticholinergic drug. In a subsequent experiment to test the interaction between scopolamine and baclofen using a nonlearned behavior, baclofen (1.25 and 2.5 mg/kg) did not affect motor activity, whereas all doses of scopolamine (0.188-0.75 mg/kg) increased activity. The higher dose of baclofen attenuated scopolamine-induced hypermotility by 50%, but the lower dose of baclofen was not effective. These data demonstrate pharmacological interactions between baclofen, a drug used clinically for spaticity, and a drug having anticholinergic properties.
Sidel
E S
ES
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Tilson
H A
HA
McLamb
R L
RL
Wilson
W A
WA
Swartzwelder
H S
HS
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D012601:Scopolamine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D012601:Scopolamine; D001418:Baclofen