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Vol. 282, Issue 3, 1526-1532, 1997
Department of Pharmacology and Experimental Therapeutics, Louisiana
State University Medical Center, New Orleans, Louisiana
The effects of cannabinoid ligands were studied in rats responding
under a repeated acquisition procedure. Each session rats were required
to learn a different three-response sequence; every third correct
completion of the sequence resulted in the presentation of a food
pellet. Errors produced a brief timeout but did not reset the chain.
Neither injections of the centrally inactive cannabinoid, cannabidiol
(3.2-100 mg/kg i.p.), nor the endogenous ligand, anandamide (0.01-18
mg/kg i.p.), affected rate or accuracy of responding. In contrast,
9-tetrahydrocannabinol (3.2-18 mg/kg i.p.) and the
long-acting analog of the endogenous ligand, R-methanandamide (1-18
mg/kg i.p.), produced dose-related increases in the total percentage of
errors and decreases in the rate of responding. The brain cannabinoid receptor antagonist SR141716A (1-32 mg/kg) did not affect either accuracy or rate of responding when administered alone. A low dose of
SR141716A (1 mg/kg), which had no effect when administered alone,
antagonized the disruptive effects of
9-tetrahydrocannabinol and R-methanandamide on rate and
accuracy of responding and produced an estimated 3-fold shift to the
right in the dose-effect curves. However, administration of SR141716A did not alter the effects of morphine. These results suggest that cannabinoid agonists produce disruptions of learning in rats through stimulation of the cannabinoid receptor. The data further suggest that
whereas cannabimimetic agents can disrupt learning, the
anandaminergic system may not be tonically involved in learning.
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