Defense Date

2013

Document Type

Thesis

Degree Name

Master of Science

Department

Pharmacology & Toxicology

First Advisor

Dana Selley

Abstract

CB1 cannabinoid receptors are G-protein-coupled receptors that mediate the central nervous system (CNS) effects of marijuana and endocannabinoids. Recently, cannabinoid receptor interacting protein 1a (CRIP1a) was discovered as a novel protein that binds to the CB1 receptor C-terminus and inhibits CB1 receptor activity without affecting CB1 expression. This thesis investigated the functions of CRIP1a by characterizing the first CRIP1a knockout (KO) mouse line. The absence of CRIP1a was confirmed in KO mice using quantitative PCR and immunoblotting. I hypothesized that CRIP1a KO mice would exhibit enhanced CB1 receptor-mediated G-protein activity in the CNS, as well as cannabimemetic phenotypes and enhanced sensitivity to cannabinoid agonists in vivo. Results showed increased CB1 agonist-stimulated G-protein activity in the amygdala of CRIP1a KO relative to WT mice, but not in cerebellum, hippocampus or spinal cord. CB1 receptor levels did not differ between genotypes in in any region examined. Interestingly, CRIP1a KO mice exhibited an anxiolytic-like phenotype and decreased nociceptive sensitivity in vivo, but did not differ from WT mice in tests of motor activity or coordination. Surprisingly, sensitivity to agonist-induced antinociception, hypothermia, catalepsy or motor incoordination did not differ between genotypes. Our findings suggest that CRIP1a could play a selective role in modulation of anxiety by endocannabinoids, and this action could be mediated through the amygdala. Thus, CRIP1a might serve as a future pharmacological target for studying and treating anxiety disorders.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

October 2013

Available for download on Wednesday, October 10, 2018

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