While marijuana remains the most widely used illicit drug in the U.S., the consequences of its use on systems of learning and memory remain poorly understood. Thus, the primary purpose of these experiments is to investigate the mechanisms by which THC, the primary psychoactive ingredient in marijuana, exerts its disruptive effects of learning and memory. First, these experiments will compare the effects of THC with those of methadamide, a synthetic analog of the endogenous cannabinoid anandamide chosen for its relatively greater metabolic stability, on acquisition, reference memory, and working memory of mice in the Morris water maze. Secondly, the receptor mechanism of action will be investigated with the CB1 receptor antagonist SR1417116A, as well as by assessing the affects of these drugs in CB1 receptor knockout mice. Finally, the putative involvement of GABA-ergic mechanisms will be assessed by evaluating the ability of drugs that differentially modulate GABAergic transmission to potentiate/attenuate the dose-effect relationships of THC and methanandamide.
