ELECTROPHYSIOLOGY OF CANNABINOID ACTION ON RAT BEHAVIORS

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This research proposal is aimed at elucidating the fundamental neuronal mechanism(s) underlying the central effects of marijuana abuse with special emphasis on the neuronal processes involved in timing, sensory-motor integration, and learning and memory process. A substantial amount of evidence has indicated marijuana profoundly disrupts locomotor and timing response, as well as learning and memory ability in human. Using a newly developed technique, 20-47 single neuronal spike trains can now be recorded concurrently in different brain areas of rats during a variety of behavior tasks. The medial prefrontal cortex (MPF), striatum and substantia nigra pars reticulate (NTR) are selected for investigation based on the neuroanatomical and behavioral evidence that these three areas contain a high density of cannabinoid receptor and are critically involved in locomotor and cognitive functions required for the tasks studied. Rats will be trained to perform delayed match/non-match to sample (DMTS/DNMTS), temporal response differentiation (TRD), reaction time (RT), and auditory-cued treadmill locomotion (TM) tasks. DMTS is the task designed to estimate the cognitive procedures involved in short term memory and spatial discrimination functions. TRD will examine the capability of the animal to estimate the passage of subjective time and to make a motor response accordingly. The RT schedule tests the ability of promptly withdrawing from nosepiece in response to trigger tone. TM is the task combining auditory tone and treadmill to test the linkage between a sensory cue (tone) and onset locomotor function. In addition, the effect of different doses of cannabinoid on spontaneous locomotor activity (from hyper-activity to catalepsy in response to different does of cannabinoid) will be investigated. An increasing dose of delta-9-tetrahydrocannabinol (delta-9-THC), the active component of marijuana,will be tested (0.5 mg to 10 mg/kg i.p.). The investigation will determine changes of neuronal activity and behavioral performance under delta-9-THC intoxication. Data analyses include computation of raster and perievent histrograms around behavioral time events. Correlationed and synchronized activities between neurons within the same region and across different regions. Ensemble activity of many neurons in relation to behavioral events will be examined using discriminant analysis. The goal of this research is to test the hypothesis that cannabinoids act to selectively disrupt component signals within the cortico-striatal system.