Neuroscience 2005 Abstract
| Presentation Number: | 227.7 |
|---|---|
| Abstract Title: | The CB1 receptor antagonist AM 251 attenuates cocaine-triggered reinstatement of drug-seeking behavior by a glutamate-, but not a DA-, dependent mechanism in rats. |
| Authors: |
Xi, Z. X.*1
; Peng, X. Q.1
; Gilbert, J.1
; Pak, A. C.1
; Gardner, E. L.1
1Behavioral Neuroscience Research Branch, National Inst. on Drug Abuse, Baltimor, MD |
| Primary Theme and Topics |
Disorders of the Nervous System - Addiction and Drugs of Abuse -- Addiction: Treatment |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Addiction and Drugs of Abuse<br />-- Addiction: Behavioral pharmacology |
| Session: |
227. Addiction Treatment: Novel Mechanisms Poster |
| Presentation Time: | Sunday, November 13, 2005 10:00 AM-11:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # VV70 |
| Keywords: | Cannabinoid, Addiction, GABA, Relapse |
Cannabinoid CB1 receptor antagonists not only block the rewarding effects of delta-9-THC, heroin, nicotine, cocaine, and ethanol, but also prevent relapse to the use of various drugs of abuse, including cocaine, heroin, and methamphetamine (see review by Le Foll and Goldberg, 2005), suggesting a potential use of CB1 receptor antagonists in treatment of drug abuse. However, the neurochemical mechanisms underlying these actions remain poorly understood. Here, we investigated the effects of the novel CB1 receptor antagonist AM 251 on cocaine-induced changes in neurotransmitter release in the nucleus accumbens in rats during reinstatement of drug-seeking behavior. We found that: 1) systemic administration of AM 251 (1, 3, 10 mg/kg i.p., 30 min prior to cocaine injection) significantly attenuates (maximally ~50%) cocaine (10 mg/kg i.p.)-triggered reinstatement of cocaine seeking; 2) acute cocaine (10 mg/kg i.p.) priming injections significantly increase extracellular DA (+160%) and glutamate (+80%), but not GABA levels in the nucleus accumbens in rats during reinstatement, while pretreatment with AM 251 (1, 3, 10 mg/kg) selectively blocks cocaine-induced phasic increases in glutamate, but not DA, levels in the nucleus accumbens; 3) AM 251 alone (1, 3, 10 mg/kg) dose-dependently elevated (+50%) extracellular glutamate and GABA levels for 2-3 hrs, but had no effect on extracellular DA levels. These data suggest that cocaine-induced increases in both DA and glutamate play an important role in cocaine-triggered relapse, and blockade of cocaine-induced increases in glutamate by AM 251 partially attenuates cocaine-triggered reinstatement of drug-seeking behavior. This blockade of cocaine-induced increases in glutamate appears to be correlated with AM 251-induced increases in extracellular glutamate and GABA levels, which may inhibit presynaptic glutamate release by activating metabotropic glutamate autoreceptors and GABAB heteroreceptors, respectively.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
Copyright © 2005-2025 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
