Biphasic effects of Δ9-tetrahydrocannabinol on brain stimulation reward and motor activity

Int J Neuropsychopharmacol. 2013 Nov;16(10):2273-84. doi: 10.1017/S1461145713000709. Epub 2013 Jul 5.

Abstract

Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the main psychoactive ingredient of marijuana, has led to equivocal results when tested with the intracranial self-stimulation (ICSS) procedure or the open-field test for motor activity, two behavioural models for evaluating the reward-facilitating and locomotor stimulating effects of drugs of abuse, respectively. Therefore, in the present study, the effects of high and low doses of Δ(9)-THC were compared in the ICSS procedure and the open-field test. Moreover, the involvement of CB(1) receptors in tentative Δ(9)-THC-induced effects was investigated by pre-treating the animals with the CB(1) receptor antagonist SR141716A (rimonabant). The results obtained show that low doses of Δ(9)-THC induce opposite effects from high doses of Δ(9)-THC. Specifically, 0.1 mg/kg Δ(9)-THC decreased ICSS thresholds and produced hyperactivity, whereas 1 mg/kg increased ICSS thresholds and produced hypoactivity. Both effects were reversed by pre-treatment with SR141716A, indicating the involvement of CB(1) receptors on these actions. Altogether, our results indicate that Δ(9)-THC can produce acute activating effects in locomotion that coincide with its reward-facilitating effects in the ICSS paradigm. The present findings provide further support that Δ(9)-THC induces behaviours typical of abuse and substantiate the notion that marijuana resembles other drugs of abuse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / metabolism
  • Cannabinoid Receptor Agonists / pharmacology*
  • Cannabinoid Receptor Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology*
  • Electric Stimulation
  • Male
  • Motor Activity / drug effects*
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / drug effects
  • Receptor, Cannabinoid, CB1 / metabolism
  • Reward*
  • Rimonabant
  • Self Stimulation / drug effects*
  • Time Factors

Substances

  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Dronabinol
  • Rimonabant