Systemic Blockade of the Endocannabinoid System Alters Gene Expression and acquisition of a Hippocampus Dependent Learning Task

Thesis under the direction of Robert Hampson, Ph.D., Associate Professor of Physiology and Pharmacology It has been established that the administration of Δ9-THC and other cannabinoid agonists results in disruptions in learning and memory (Sullivan, 2000). The ability of rimonabant to reverse memory deficits induced by cannabinoid agonists lead to the hypothesis that administering it alone could induce learning and memory enhancements (Brodkin and Moerschbaecher, 1997). Rimonabant-induced memory enhancements may be mediated via alterations in cellular mechanisms, such as gene expression, that influence the manifestation of learning and memory. Few studies have assessed the global and specific role of the cannabinoid system in altering gene expression. The current study examined the effect of continuous CB1 receptor antagonism on the expression of genes that influence learning and memory in the hippocampus as well as the ability of rimonabant to improve learning using a delayed non-match to sample (DNMS) task. Male Long–Evans rats received continuous subcutaneous rimonabant infusions via an Alzet osmotic mini-pump for 28 days. Rats pre-trained to perform the DNMS task at a 0 sec delay required more days to learn the delay component of the task. In rats that received continuous rimonabant with no training it was found that rimonabant treatment increased the expression of genes that influence learning and memory in the hippocampus. These results suggest that continuous rimonabant administration increase the potential for synaptic plasticity events to occur however, judging from the results of the DNMS task that potential did not result in an increased ability to learn.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2010

Author dc:creator

• Horton, Kofi-Kermit

• Endocannabinoid System

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10339/14932

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/14932