CHRONIC TREATMENTS WITH CHOLINOCEPTOR DRUGS INFLUENCE SPATIAL-LEARNING IN RATS

Nicotine, scopolamine. oxotremorine, di-isopropyl-fluorophosphate (DFP ) and tetrahydroaminoacridine (THA) were administered chronically to d ifferent groups of rats in doses reported to alter central muscarinic and/or nicotinic receptor numbers. Beginning 24 h after final drug inj ection, the groups were compared to a vehicle control group on acquisi tion of a hidden platform position in the Morris water maze over 20 tr ials with a 30-min inter-trial interval. Chronic treatment with either nicotine or scopolamine significantly improved the rate of learning, but oxotremorine and DFP retarded learning and THA had no effect on le arning. The chronic drug effects on behaviour were consistent with kno wn effects of the injected drugs on muscarinic and nicotinic binding i n the forebrain and on the sensitivity of frontal cortex neurones to i ontophoretically applied cholinoceptor agonists. However, alternative explanations for the observed changes cannot be ruled out. since the d rugs used are known to have a wide range of effects on other neurotran smitters.