The behavioral effects of serotonin synthesis inhibition and quisqualic acid induced lesions of the nucleus basalis magnocellularis in rats.

1. To investigate the role of the cholinergic and serotonergic systems in the regulation of cognitive functions, the effects of concurrent lesioning of nucleus basalis magnocellularis (NB) with quisqualic acid (quis) and inhibition of brain serotonin synthesis by systemic p-chlorophenylalanine (PCPA) treatment on passive avoidance (PA) retention and water maze (WM) spatial navigation performance were studied in rats. 2. Quis NB lesioning induced a marked reduction (-62%) in frontal cortical choline-acetyltransferase activity, impaired retention of PA, and slightly and transiently impaired acquisition of WM spatial navigation. 3. PCPA (400 mg/kg/day x 3, i.p.) treatment depleted frontal cortical concentrations of both serotonin (82% depletion) and its major metabolite 5-HIAA (90% depletion) and slightly affected the noradrenergic and dopaminergic systems. PCPA treatment alone had no effect on WM or PA behavior, but potentiated the PA retention deficit and slightly aggravated the WM deficit in rats subjected to quis NB lesioning. 4. The present results further support the view that serotonergic and NB neurons interact in the regulation of cognitive functions.