Effects of combined block of alpha(1)-adrenoceptors and NMDA receptors on spatial and passive avoidance behavior in rats

The present study was designed to investigate the interactions between alpha(1)-adrenoceptors and NMDA receptors in modulating spatial navigation and passive avoidance behavior in rats. Pretraining treatment with prazosin, an alpha(1)-adrenoceptor antagonist, at 2 mg/kg i.p., impaired acquisition performance in a water maze navigation test and had no effect on passive avoidance behavior. Posttraining and pretest injections of prazosin had no effect on water maze or passive avoidance behavior. Pretraining treatment with ((+/-))-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a competitive NMDA receptor antagonist, dose dependently (3 and 10 mg/kg) impaired passive avoidance and water maze behavior. Posttraining treatment with CPP had no effect on water maze and passive avoidance behavior. A pretraining combination of subthreshold doses of CPP (1 mg/kg) and prazosin (1 mg/kg) impaired water maze behavior. A combination of subthreshold doses of CPP (3 mg/kg) and prazosin (1 mg/kg) injected posttraining or pretest had no marked effect on water maze or passive avoidance performance. A control experiment showed that CPP 3 mg/kg or CPP 1 mg/kg and prazosin 1 mg/kg injected pretraining had no effect on cue navigation to a clearly visible platform, but CPP 10 mg/kg markedly impaired performance. The present results indicate that alpha(1)-adrenoceptors and NMDA receptors may synergistically regulate acquisition of spatial navigation performance. ?Therefore, it would be interesting to study the effects of combined stimulation of alpha(1)-adrenoceptors and NMDA receptors on age-related memory defects.