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Abstract

A detailed behavioural analysis of water maze spatial performance in the rat was utilized to determine the effect of single and combined administration of p-chlorophenylalanine (PCPA; 1000 mg/kg, i.p.), an inhibitor of serotonin biosynthesis, and scopolamine hydrobromide (SCO; 1.0 mg/kg, i.p.), a muscarinic receptor antagonist. In some groups a water maze pretraining regimen known as non-spatial pretraining (NSP) was used to familiarize the animals with the general requirements of the task before spatial training was begun. The results showed that: (a) depletion of serotonin with PCPA had no effect on water maze performance and produced no sensorimotor disturbances; (b) antagonism of muscarinic receptors produced impairments in spatial and sensorimotor function in naive rats but neither effect was observed in rats first given NSP; (c) combined disruption of muscarinic and serotonergic function produced a severe deficit in spatial performance that was only partially alleviated by NSP; and (d) there was an association between poor maze acquisition scores and a high incidence of sensorimotor dysfunction. In addition to the water maze task the rats were also assessed for motoric performance on a beam walking test. The role of cholinergic and serotonergic systems in learning and memory is discussed.