Research is described in this application to continue investigations of the effects of delta-9-THC, the psychoactive derivative of marijuana, on neurobehavioral mechanisms involved in the perception, registration, and retrieval of trial specific sensory information of rats. Past research accomplished in the last funding period has indicated that behavioral tasks sensitive to destruction of the hippocampus and related brain regions are disrupted in dose-dependent fashion by delta-9-THC. Concomitant recording of hippocampal electrical activity in the form of well characterized sensory evoked potentials and cellular discharges were also disrupted by the same dose levels of delta-9-THC. Experiments are proposed to continue research in two main areas of behavioral influence of delta-9-THC initiated in the last funding period: 1) evaluation of effects of delta-9-THC on perceptual processes utilizing signal detection methodology in order to evaluate delta-9-THC produced deficits in registration of sensory information, and in separate but parallel experiments 2) investigation of the selective influence of delta-9-THC on the registration and retrieval of trial specific information in behavioral tasks which require hippocampal involvement utilizing delayed match to sample and variations of those behavioral paradigms. In these studies, neural correlates of successful behavioral performance have been and will continue to be examined in terms of dose-dependent influences of delta-9- THC. A major purpose of the project is to isolate and characterize neurobehavioral events which are 1) critically involved with information processing as indicated above, and 2) selectively influenced in """"""""dose- dependent"""""""" manner by acute doses of delta-9-THC. Further extension of this research initiated in the last funding period includes evaluation of the above described behavioral and electrophysiological endpoints following chronic exposure to delta-9-THC over a 35-day treatment period. Preliminary evidence indicates a differential timecourse of tolerance development in the above behavioral measures. This suggests that there exists a hierarchy of sensitivity of neurobehavioral mechanisms to long term or repeated exposure to delta-9-THC which cannot be predicted from reactivity exhibited following a single acute injection.
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