(+/-)Baclofen sensitive scopolamine-induced short-term memory deficits in mice.
Possible involvement of GABA receptor systems in scopolamine-induced short-term memory deficits was investigated using latency of mice to reach shock-free zone (SFZ) and number of mistakes (descents) the animal made in 15 min as parameters for acquisition and retention of memory in passive avoidance paradigm. Atropine (1-5 mg/kg), scopolamine (0.1-0.5 mg/kg) but not pirenzepine (5-20 mg/kg) caused disruption of memory. GABA (50, 75 and 100 mg/kg) showed retention enhancing effects in scopolamine-treated and untreated animals but GABA agonist progabide (5-20 mg/kg) did not affect any of the parameter significantly. GABAA agonist, muscimol (0.05 and 0.1 mg/kg) and GABAB agonist, (+/-)baclofen (0.25, 0.5 and 1 mg/kg) and (-)baclofen (0.25 and 0.5 mg/kg) also displayed memory enhancing action. Whereas, GABAA antagonist, bicuculline produced hind limb rigidity, GABAB antagonist, CGP 35348 did not show any effect per se, but reversed the (+/-)baclofen-induced delay in latency, without affecting retention enhancing action of (+/-)baclofen. Combined administration of subeffective dose of GABA (50 mg/kg) and (+/-)baclofen (0.25 mg/kg), showed a significant improvement in acquisition and retention. However, the effect of GABA (100 mg/kg) on acquisition was reversed by bicuculline (2 mg/kg) and by CGP 35348 (100 mg/kg) while improving retention. The present study extends support to the cholinergic concept in cognitive performance and provide an evidence for the influence of GABAergic (particularly GABAB) modulation in scopolamine-induced learning and memory deficits in mice.
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
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AC
Sharma
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Kulkarni
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348; D012601:Scopolamine; D001418:Baclofen