Neuroscience 2004 Abstract
| Presentation Number: | 690.17 |
|---|---|
| Abstract Title: | Chronic cannabinoid neuroprotection in the <I>spastic</I> Han Wistar rat: Mediated by altered CB1 receptor expression? |
| Authors: |
Iniguez, J. A.*1
; Ochoa, A. E.1
; Cohen, R. W.1
1Dept Biol., CA State Univ - Northridge, Northridge, 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 8:00 AM-9:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # EEE10 |
| Keywords: | Cerebellum, Hippocampus, Excitotoxicity, Neurodegeneration |
Many studies have shown that the active components of marijuana (cannabinoids) may exhibit neuroprotective properties. Both exogenous and endogenous cannabinoids bind to CB1 receptors found in several areas of the brain, including the cerebellum and hippocampus. Our study investigated the potential neuroprotective properties of cannabinoids on the spastic Han Wistar rat (sHW). Neurodegeneration in the cerebellum and hippocampus cause the sHW rat to exhibit hyperactivity, fore limb tremor, and hind limbs ataxia, leading to death at 65 days. To examine changes in CB1 receptor expression in the sHW rats, slices from mutant and normal siblings were processed for immunohistochemistry. At 30 days of age, there were no staining differences between the mutant and normal rats in any sections. In 60 day mutant hippocampus sections, an increase in CB1 expression was seen in the striatum oriens, indicating possible reorganization of the hippocampus. In 60 day mutant cerebellar sections, despite substantial Purkinje cell loss, the remaining somas and dendrites stained heavier than in the normals. To examine the pharmacological effects of the altered expression, mutants and normal siblings were treated acutely (5mg/kg) with one of three agonists, anandamide (n=13), R-(+)-Win 55,212-2 (n=14) and methanandamide (n=22) or the cannabinoid antagonist SR141716A (n=12). The control groups (n=44) received vehicle (DMSO or ethanol). The injections were administered intraperitoneally twice a week on nonconsecutive days. Lack of change in the longevity under treatment with any drugs indicated these drugs provide limited neuroprotection for the sHW mutant. Chronic infusion of the agonist methanandamide using osmotic pumps (Durect Inc.) had significant effects: a 20% increase in longevity by sHW mutants treated with methanandamide. In addition, treatment with agonist R-(+)-Win 55212-2 did slow the rate of motor impairment, suggesting possible neuroprotection in the cerebellum.
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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