The objective of Project #3 'Consequences of chronic exposure to A9-tetrahydrocannabinol inmonkeys' is to further the goals of the P20 center by establishing a model of adolescent cannabis exposurein nonhuman primates. The studies propose to examine the neurobehavioral and neurochemical sequelae ofchronic exposure to A9-tetrahydrocannabinol (THC) in peri-adolescent rhesus monkeys. The model offers aunique translational bridge across the Center Projects because monkeys will be studied across theadolescent (Proj #2) to young adult (Proj #1) developmental stages, will be examined on tasks identical inmany cases to the human tasks and can be exposed to specific drug models informed by Proj #4 rodentresults.
The first Aim i s to determine the effects of chronic THC exposure on neuropsychological test batterymeasures (CANTAB) long established in the laboratory. The acquisition and performance of tasks whichmeasure attentional shift, spatial memory, recognition memory, decision making motor function andmotivation will be compared between animals chronically exposed to THC for 2 years and vehicle-exposedmonkeys. Since CANTAB measures will also be employed in Proj #1 and #2, and analogous tasks used inthe rodent Proj #4, the results from the monkeys will be used to refine the specificity of the behavioralmeasures for all projects. Periodic cerebrospinal fluid sampling will be employed throughout chronic dosingto monitor neurochemical sequelae of chronic exposure.
The second Aim i s to determine the effects ofwithdrawal from chronic THC exposure on behavior, neurochemistry and physiology; antagonist challenge(SR141716A) and spontaneous (28 day) withdrawal approaches will be examined.
The fourth Aim i s todetermine the effects of chronic THC exposure on brain activation using functional Magnetic ResonanceImaging. This f MRI approach is developmental in nature and will be informed by ongoing results from Proj#1 and #2. In total, the studies proposed will address questions regarding the impact of chronic exposure tothe primary psychoactive constituent of cannabis and the behavioral specificity, neurochemical andneurovascular sequelae of chronic THC in monkeys will be determined. These studies will also establish aperi-adolescent model of cannabis exposure with tremendous potential for further translational studies in aneventual full Center.
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