An inverse agonist selective for alpha5 subunit-containing GABAA receptors improves encoding and recall but not consolidation in the Morris water maze.

Psychopharmacology
N CollinsonD N Stephens

Abstract

Compounds selective for the GABAA receptors containing an alpha5 subunit have been reported to enhance performance in the hippocampally mediated delayed-matching-to-position version of the Morris water maze, in which reduction in the time required to find a hidden platform relative to an initial trial is used as an index of learning and memory. In the present study, we have used one such compound, alpha5IA-II, to examine whether these effects occur during the encoding, consolidation or recall phases of this paradigm. alpha5IA-II was administered in the absence or presence of the benzodiazepine site antagonist flumazenil, so as to limit its action to periods associated with encoding, consolidation and recall. Drug doses and timings of administrations were defined using occupancy data derived from an in vivo [3H]flumazenil binding assay. Similar experiments were carried out to study the memory-disruptive properties of chlordiazepoxide (CDP). The trial 1 to trial 2 difference was increased when alpha5IA-II was given before either trial 1 or trial 2, indicating an effect on the encoding and recall phases, respectively, of learning and memory. Conversely, alpha5IA-II had no effect on performance when given immediately after trial 1,...Continue Reading

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Oct 22, 2008·Psychopharmacology·Theresa M BallardMaria-Clemencia Hernandez
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