β-Endorphin elevations in the ventral tegmental area regulate the discriminative effects of Δ-9-tetrahydrocannabinol

M. Solinas, A. Zangen, N. Thiriet, S. R. Goldberg

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

β-Endorphin is an endogenous opioid that produces behavioral effects similar to heroin and morphine and is released in the nucleus accumbens by cocaine, amphetamine and ethanol, suggesting a general involvement in the reinforcing effects of abused drugs. Here we show that, in rats, Δ-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, produces large increases in extracellular levels of β-endorphin in the ventral tegmental area and lesser increases in the shell of the nucleus accumbens. We then used a two-lever choice THC-discrimination procedure to investigate whether THC-induced changes in endogenous levels of β-endorphin regulate the discriminative effects of THC. In rats that had learned to discriminate injections of THC from injections of vehicle, the opioid agonist morphine did not produce THC-like discriminative effects but markedly potentiated discrimination of THC. Conversely, the opioid antagonist naloxone reduced the discriminative effects of THC. Bilateral microinjections of β-endorphin directly into the ventral tegmental area, but not into the shell of the nucleus accumbens, markedly potentiated the discriminative effects of ineffective threshold doses of THC but had no effect when given alone. This potentiation was blocked by naloxone. Together these results indicate that certain psychotropic effects of THC related to drug abuse liability are regulated by THC-induced elevations in extracellular β-endorphin levels in brain areas involved in opiate reward and reinforcement processes.

Original languageEnglish
Pages (from-to)3183-3192
Number of pages10
JournalEuropean Journal of Neuroscience
Volume19
Issue number12
DOIs
StatePublished - 1 Jun 2004
Externally publishedYes

Keywords

  • Abuse
  • Cannabis
  • Drug discrimination
  • Microdialysis
  • Opioid
  • Rat THC

ASJC Scopus subject areas

  • Neuroscience (all)

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