Evidence for GABA-BZ receptor modulation in short-term memory passive avoidance task paradigm in mice.
The possible involvement of gamma-aminobutyric acid/benzodiazepine (GABA-BZ) receptor modulation in scopolamine-induced short-term memory deficit was investigated in mice. Passive avoidance step-down task behavior was observed. Latency of mice to reach shock-free zone (SFZ) and number of mistakes the animal made in 15 min were used as separate parameters for acquisition and memory retention, respectively. Scopolamine (0.3 mg/kg) caused a delay in reaching SFZ and an increased number of mistakes. Physostigmine reversed the scopolamine-induced increase in number of mistakes; however, it caused a delay in the time to reach SFZ. Subeffective dose of GABA, when combined with physostigmine, further delayed the latency to reach SFZ, but reduced the number of mistakes very significantly. GABA (50, 75 and 100 mg/kg, i.p.) and GABA agonists sodium valproate (30 and 60 mg/kg, i.p.), fengabine (5 and 10 mg/kg, i.p.), (+/-)baclofen (0.25, 0.5 and 1.0 mg/kg, i.p.) and (-)baclofen (0.25 and 0.5 mg/kg i.p.) reversed the scopolamine-induced effect; however, sodium valproate at higher dose delayed time to reach SFZ. Combined administration of lower dose (+/-)baclofen and subeffective dose of GABA showed significant decrease in latency and number of mistakes in scopolamine-treated animals. The specific benzodiazepine antagonist flumazenil (Ro-15-1788) (5 and 10 mg/kg, i.p.) and inverse agonist FG-7142 (10 mg/kg, i.p.) very significantly reversed scopolamine-induced increase in number of mistakes, but Ro-15-1788 failed to show any effect on latency per se and in scopolamine-treated experiments, as well.(ABSTRACT TRUNCATED AT 250 WORDS)
Sharma
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AC
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
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SK
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology; D004597:Electroshock; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D010830:Physostigmine / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002243:Carbolines; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C035874:FG 7142; D010830:Physostigmine; D012601:Scopolamine