Cannabidiol impairs the rewarding effects of methamphetamine: Involvement of dopaminergic receptors in the nucleus accumbens

Prog Neuropsychopharmacol Biol Psychiatry. 2022 Mar 8:113:110458. doi: 10.1016/j.pnpbp.2021.110458. Epub 2021 Oct 15.

Abstract

Cannabidiol, as component of cannabis, can potentially hinder the rewarding impact of drug abuse; however, its mechanism is ambiguous. Moreover, the nucleus accumbens (NAc), as a key area in the reward circuit, extensively receives dopaminergic projections from the ventral tegmentum area. To elucidate the role of accumbal D1 and D2 dopamine receptor families in Cannabidiol's inhibitory impact on the acquisition and expression phases of methamphetamine (MET), the conditioned place preference (CPP) procedure as a common method to assay reward characteristics of drugs was carried out. Six groups of rats were treated by various doses of SCH23390 or Sulpiride (0.25, 1, and 4 μg/0.5 μL) in the NAc as D1 or D2 dopamine receptor family antagonists, respectively, prior to infusion of Cannabidiol (10 μg/5 μL) in the lateral ventricle (LV) over conditioning phase in the acquisition experiments. In the second step of the study, animals received SCH23390 or Sulpiride in the NAc before Cannabidiol (50 μg/5 μL) infusion into the LV in the expression phase of MET to illuminate the influence of SCH23390 or Sulpiride on the inhibitory impact of Cannabidiol on the expression of MET-induced CPP. Intra-NAc administration of either SCH23390 or Sulpiride impaired Cannabidiol's suppressive impact on the expression phase, while just Sulpiride could suppress the Cannabidiol's impact on the acquisition phase of the MET-induced CPP. Also, the inhibitory impact of Sulpiride was stranger in both phases of MET reward. It seems that Cannabidiol prevents the expression and acquisition phases of MET-induced CPP partly through the dopaminergic system in the NAc.

Keywords: Cannabidiol; Conditioned place preference; Dopamine receptor family; Methamphetamine; Nucleus accumbens; Reward.

MeSH terms

  • Animals
  • Benzazepines / administration & dosage
  • Cannabidiol* / administration & dosage
  • Cannabidiol* / pharmacology
  • Conditioning, Classical*
  • Dopamine Antagonists / administration & dosage
  • Male
  • Methamphetamine / pharmacology*
  • Nucleus Accumbens / drug effects*
  • Rats
  • Receptors, Dopamine D1 / drug effects*
  • Receptors, Dopamine D2 / drug effects*
  • Reward*
  • Sulpiride / administration & dosage
  • Ventral Tegmental Area / drug effects

Substances

  • Benzazepines
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • SCH 23390
  • Cannabidiol
  • Methamphetamine
  • Sulpiride