Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common mu1 opioid receptor mechanism

Science. 1997 Jun 27;276(5321):2048-50. doi: 10.1126/science.276.5321.2048.

Abstract

The effects of the active ingredient of Cannabis, Delta9-tetrahydrocannabinol (Delta9-THC), and of the highly addictive drug heroin on in vivo dopamine transmission in the nucleus accumbens were compared in Sprague-Dawley rats by brain microdialysis. Delta9-THC and heroin increased extracellular dopamine concentrations selectively in the shell of the nucleus accumbens; these effects were mimicked by the synthetic cannabinoid agonist WIN55212-2. SR141716A, an antagonist of central cannabinoid receptors, prevented the effects of Delta9-THC but not those of heroin. Naloxone, a generic opioid antagonist, administered systemically, or naloxonazine, an antagonist of micro1 opioid receptors, infused into the ventral tegmentum, prevented the action of cannabinoids and heroin on dopamine transmission. Thus, Delta9-THC and heroin exert similar effects on mesolimbic dopamine transmission through a common mu1 opioid receptor mechanism located in the ventral mesencephalic tegmentum.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines
  • Dopamine / metabolism*
  • Dronabinol / antagonists & inhibitors
  • Dronabinol / pharmacology*
  • Heroin / pharmacology*
  • Male
  • Microdialysis
  • Morpholines / antagonists & inhibitors
  • Morpholines / pharmacology
  • Naloxone / analogs & derivatives
  • Naloxone / pharmacology
  • Naphthalenes / antagonists & inhibitors
  • Naphthalenes / pharmacology
  • Narcotic Antagonists / pharmacology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Drug / metabolism
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Receptors, Opioid, mu / metabolism*
  • Rimonabant

Substances

  • Benzoxazines
  • Morpholines
  • Naphthalenes
  • Narcotic Antagonists
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Receptors, Opioid, mu
  • Naloxone
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Heroin
  • Dronabinol
  • naloxonazine
  • Rimonabant
  • Dopamine