COGNITIVE DYSFUNCTIONS INDUCED BY SCOPOLAMINE ARE REDUCED BY SYSTEMICOR INTRAHIPPOCAMPAL MINERALOCORTICOID RECEPTOR BLOCKADE

Central cholinergic blockade with scopolamine (SCOP) produces profound cognitive impairments in human and animal subjects. We hypothesized t hat cognitive deficits induced by cholinergic blockade originate partl y from its ability to enhance reactivity to the environment, an effect that would be ameliorated by prior mineralocorticoid receptor (MR) bl ockade, because MR antagonists reduce reactivity to novelty. In the pr esent study, we investigated whether or not systemic or intrahippocamp al infusions of the MR antagonist spironolactone (SPIRO) would affect SCOP-induced cognitive impairments in a water maze task. Adult male Li ster hooded rats (350-450 g) served as subjects. In Experiment 1, rats were administered SPIRO (0 or 100 mg/kg IP) followed 10 min later by SCOP (0, 0.5, or 2.0 mg/kg IP; n = 10/group). In Experiment 2, groups of rats implanted with hippocampal cannulae received central infusions of SPIRO (50 ng/mu l; 3 mu l in total) 10 min prior to SCOP injection (2.0 mg/kg IP; n = 6/group). Behavioural testing started 15 min after SCOP administration and consisted of a simple water maze task in whic h animals were required to locate a submerged platform using spatial c ues, The testing regime consisted of two phases: a) acquisition, and b ) retention, 24 h later. Peripheral, but not central, injections of SP IRO enhanced water maze performance during acquisition in SCOP-treated rats, as shown by shorter latencies and shorter distances travelled t o locate the hidden platform. Both peripheral and central SPIRO admini stration reduced the long-term retention deficits in performance in th e SCOP-treated animals. These data are in general agreement with a gro wing body of research suggesting that corticosteroid hormones interact with central cholinergic systems to affect both physiological and beh avioural responses, MR blockade may reduce an animal's reactivity to t he environment and enable it to selectively filter out extraneous stim uli that it would otherwise react to, thus impairing performance. (C) 1997 Elsevier Science Inc.