Neuroscience 2005 Abstract
| Presentation Number: | 227.14 |
|---|---|
| Abstract Title: | The DA D<sub>3</sub> receptor antagonist SB-277011-A inhibits thc-induced increase in brain stimulation reward and extracellular DA in the nucleus accumbens of rats. |
| Authors: |
Gilbert, J. G.*1
; Xi, Z. X.1
; Peng, X. Q.1
; Pak, A. C.1
; Ashby Jr, C. R.2
; Heidbreder, C. A.3
; Gardner, E. L.1
1Intramural Research Program, National Inst. on Drug Abuse, Baltimore, MD 2NY, 5500 Nathan Shock Dr., 21224, Jamaica 3USA, 5500 Nathan Shock Dr., 21224, Jamaica |
| 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 />-- Cannabinoids |
| Session: |
227. Addiction Treatment: Novel Mechanisms Poster |
| Presentation Time: | Sunday, November 13, 2005 9:00 AM-10:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # VV70 |
| Keywords: | cannabinoid, addiction, reinforcement, accumbens |
Marijuana is the most widely used illicit substance in the USA, and there is no effective medication available to treat marijuana abuse. Delta-9-tetrahydrocannabinol (THC), the active constituent in marijuana, significantly stimulates the brain mesolimbic dopamine (DA) system and enhances brain stimulation reward. We have previously shown that blockade of brain DA D3 receptors by SB-277011A significantly attenuates cocaine- or nicotine-enhanced brain reward, cocaine self-administration, cocaine- or heroin-conditioned place preference, and cocaine- or nicotine-induced reinstatement of drug-seeking behavior (Heidbreder, et al, 2005). In the present study, we investigated whether SB-277011A inhibits THC-enhanced brain stimulation reward and THC-induced increase in DA in the nucleus accumbens. THC (0.25 mg/kg i.p.) reliably shifted brain-reward stimulation curves to the left, lowering stimulation thresholds by around 15% in male Lewis rats. SB-277011A (3-12 mg/kg i.p., 1 hour prior to THC) dose-dependently blocked THC-enhanced brain stimulation reward. Using in vivo microdialysis, we further found that THC (1 mg/kg i.p.) significantly increased (~50%) extracellular DA in the nucleus accumbens. SB-277011A alone (12-24 mg/kg i.p.) dose-dependently lowered (~50%) extracellular DA levels for 3-4 hrs. Pretreatment with the same doses of SB-277011A almost completely blocked THC-induced increases in extracellular DA. Taken together, these data suggest that DA D3 receptors play an important role in marijuana’s rewarding effects, and that SB-277011A or other D3-selective antagonists may be effective in treatment of marijuana abuse, at least partially by inhibiting THC-induced DA release in the nucleus accumbens.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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