Drugs of abuse are associated with a variety of cognitive deficits including disruption of learning and memory. This is a particular concern with respect to the so-called """"""""club drugs"""""""" such as methylenedioxymethamphetamine (MDMA) and methamphetamine. A major difficulty in characterizing the nature of such impairments is to separate the drug's effect on learning from more general performance decrements. The goal of the proposed research is determine the effects of several of the club drugs on learning using a rat model that brings the methodological sophistication of the repeated acquisitions technique to the study of spatial navigation in the Morris Swim Task, a two-dimensional analogue of the Morris Task, and olfactory discrimination learning. In the repeated acquisitions procedure, drug effects on a well-learned problem can be compared directly with acquisition of a new problem. Experiment 1 will determine the effects of the MDMA, methamphetamine, and methylphenidate on acquisition of spatial navigation (Morris Swim Task) in rats. Experiment 2 will evaluate the effects of the same three drugs using a touch-screen apparatus to study repeated acquisition of visual discrimination learning problems. Experiment 3 will study these drugs using an olfactory discrimination learning procedure. In all three sets of studies, the acute effects of moderate drug doses will be determined and the residual effects of potentially neurotoxic high doses will also be evaluated. Finally, the same procedures will be used to evaluate the effects of NMDA antagonists phencyclidine, dizocilpine and LY235959 (Experiments 4 & 5). An overarching goal of the project is to continue to develop and evaluate the utility of these new methodologies as tools in the assessment of drug effects on learning.
