2R,4R-APDC influence on hypoxia-induced impairment of learning and memory processes in passive avoidance test.

Abstract

We investigated the effects of 2R,4R-APDC, a selective group II metabotropic glutamate receptor (II mGluR) agonist, on certain behaviors in rats subjected and non-subjected to hypoxia. Short-term hypoxia was used as a model of experimentally induced amnesia. 2R,4R-APDC given intracerebroventricularly (icv) at doses of 1 mumol and 100 nmol decreased the number of crossings and rearings in the open field, impaired acquisition and consolidation but improved retrieval in the passive avoidance tests. It also shortened the time spent in open arms and prolonged the time spent in closed arms, reduced the number of open and closed arms entries in an elevated "plus" maze, which is a measure of anxiety. Four-minute hypoxia (2% O(2), 98% N(2)) retrieval of conditioned responses, and exhibited an anxiogenic effect in the elevated "plus" maze in rats, i.e. it reduced the time spent in open arms and the number of entries to closed and open arms. 2R,4R-APDC effect on locomotor and exploratory activity was not changed after hypoxia, i.e. we observed inhibition of motility. This agonist of II mGluRs used at both doses before hypoxia significantly improved acquisition and retrieval, and had dual effect on consolidation, viz. at a dose of 1 mumol, it impaired this process and at a dose of 100 nmol it improved it. In the elevated "plus" maze, rats pretreated with 2R,4R-APDC and then subjected to hypoxia shortened the time spent in open arms and prolonged the time spent in closed arms, reduced the time spent in open arms, i.e. the drug exhibited anxiogenic effect. We conclude, therefore, that 2R,4R-APDC itself impaired acquisition and consolidation, enhanced retrieval but in rats undergoing hypoxia, it improved acquisition, retrieval and when used at the dose of 100 nmol enhanced consolidation. 2R,4R-APDC had beneficial effect in hypoxia-induced memory impairment in passive avoidance test.