Neuroscience 2003 Abstract
| Presentation Number: | 723.9 |
|---|---|
| Abstract Title: | The subjective response to delta-9-tetrahydrocannabinol (THC) is modulated by activation of endogenous opioid systems in rats. |
| Authors: |
Solinas, M.*1,2
; Zangen, A.2
; Pappas, L. A.1,2
; Goldberg, S. R.1,2
1PreClin. Pharmacol. Section, NIDA, Baltimore, MD 2Behavioral Neurosci. Br., NIDA, Baltimore, MD |
| Primary Theme and Topics |
Cognition and Behavior - Motivation and Emotion |
| Secondary Theme and Topics | Synaptic Transmission and Excitability<br />- Neurotransmitters<br />-- Opioid |
| Session: |
723. Motivation & Emotion Poster |
| Presentation Time: | Tuesday, November 11, 2003 1:00 PM-2:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # J8 |
| Keywords: | CANNABINOIDS, DRUG DISCRIMINATION, BETA-ENDORPHIN, VTA |
Several pharmacological effects of delta-9-tetrahydrocannabinol (THC) are reduced or blocked by administration of opioid antagonists and rewarding or aversive properties of THC are modified in mice lacking opioid receptors. In this study, rats learned to discriminate a 3 mg/kg i.p. injection of THC from an injection of vehicle under a two-lever choice procedure with food reinforcement. We then investigated whether the subjective effects of THC could be blocked or reduced by administration of opioid antagonists and whether opioid agonists could mimic or potentiate THC’s subjective effects. The opioid antagonist naloxone (1 mg/kg, i.p.) produced a small decrease in the discriminative effects of the training dose of 3 mg/kg THC and significantly shifted the THC dose-response curve to the right. When the opioid agonist morphine (1-10 mg/kg, i.p.) was substituted for THC, it did not produce THC-like discriminative effects. However, a 1 mg/kg dose of morphine potentiated the discriminative effects of THC, shifting the THC dose-response curve to the left. Using in-vivo microdialysis, we found that the 3 mg/kg dose of THC, which served as the training stimulus for the drug-discrimination study, significantly increased extracellular levels of the endopioid beta-endorphin in the Ventral Tegmental Area (VTA), the origin of the dopaminergic mesolimbic system and a major brain area involved in reinforcing effects of opioids. Finally, bilateral microinjections of beta-endorphin directly into the VTA potentiated the discriminative effects of a threshold 1 mg/kg dose of THC. Thus, the subjective effects of THC appear to be markedly modulated by release of beta-endorphin and activation of opioid receptors in the VTA, an area involved in opioid reward and reinforcement.
Supported by NIDA, NIH, DHHS
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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