Neuroscience 2004 Abstract
| Presentation Number: | 690.10 |
|---|---|
| Abstract Title: | PKC epsilon null mice show enhanced behavioral responses to cannabinoids. |
| Authors: |
Wallace, M. J.*1
; Newton, P. M.1
; Messing, R. O.1
1Ernest Gallo Clin. and Res. Ctr., Univ California, SF, Emeryville, CA |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Addiction and Drugs of Abuse -- Cannabinoids |
| Session: |
690. Drugs of Abuse: Cannabinoids Poster |
| Presentation Time: | Tuesday, October 26, 2004 9:00 AM-10:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # EEE10 |
| Keywords: | ANALGESIA, HYPOTHERMIA, KNOCKOUT, KINASE |
Endocannabinoids and Δ9-tetrahydrocannabinol, the major psychoactive compound in marijuana, bind to and activate the cannabinoid CB1 receptor. The CB1 receptor is the most abundant G-protein coupled receptor in brain, with high levels of expression in the hippocampus, striatum, cortex and reward centers of the basal ganglia. Activation of CB1 leads to decreased excitatory and inhibitory neurotransmitter release in several brain regions through activation of GIRK channels and inhibition of voltage-gated calcium channels. In vivo responses to cannabinoid receptor agonists have been generally measured using four behavioral assays; hypothermia, spontaneous activity, analgesia and catalepsy. Despite its abundance in the brain, little is known about mechanisms that modulate CB1 receptor signaling. Here we show that PKCε, a member of the novel subclass of PKC isozymes, mediates behavioral sensitivity to both endogenous and exogenous cannabinoids. In these studies, PKCε null mice showed enhanced analgesia and hypothermia in response to WIN55212-2 (0.5 and 2.5 mg/kg) compared to wild-type littermates. Additionally, PKCε null mice displayed marked hypothermia following administration of the endogenous cannabinoid anandamide (50 mg/kg) while wild-type littermates did not. These findings suggest that PKCε is a novel regulator of the neuromodulatory endogenous cannabinoid system.
Supported by NIH Grant AA13588
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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