Microstructure analysis of the effects of the cannabinoid agents HU-210 and rimonabant in rats licking for sucrose

Eur J Pharmacol. 2020 Nov 15:887:173468. doi: 10.1016/j.ejphar.2020.173468. Epub 2020 Aug 8.

Abstract

Stimulation of cannabinoid CB1 receptors generally increases ingestion. However, the non-selective cannabinoid receptor agonist HU-210 exerts the opposite effect. The first objective of this study was to investigate the role of CB1 receptors in this "atypical" effect. Studies on the endocannabinoid system investigating the microstructure of licking for palatable solutions reported inconsistent results as for the role of CB1 receptors in "liking" and "wanting". The second objective was to deal with these inconsistencies investigating the within-session time-course of licking-burst number. The microstructure of licking for a 10% sucrose solution in 30-min sessions was analysed in two experiments. In Experiment 1, the effect of the CB1 receptor antagonist-inverse agonist rimonabant (0.5, 1 mg/kg) on HU-210 effect (100 μg/kg) was investigated. A dose range of HU-210 (25, 50, 100 μg/kg) was examined in Experiment 2. In Experiment 1, both HU-210 and rimonabant reduced licking due to reduced burst number. Moreover, HU-210 reduced the intra-burst lick rate, an index of motor competence. HU-210 effects were antagonised by rimonabant, and vice versa. Rimonabant decreased burst number late in the session at 0.5 mg/kg, and since the beginning of the session at 1 mg/kg. In Experiment 2, HU-210 failed to affect overall ingestion. These results suggest that HU-210 effect - when present - depends on CB1 receptor stimulation, possibly leading to impairment of the motor competence necessary for licking. The reduction of burst number late in the session observed with rimonabant 0.5 mg/kg, which resembles the effect of reward devaluation, might suggest reduced "liking".

Keywords: Behavioural activation; HU-210; Licking microstructure; Reward; Reward-evaluation; Rimonabant.

MeSH terms

  • Animals
  • Cannabinoid Receptor Antagonists / pharmacology*
  • Dose-Response Relationship, Drug
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Feeding Behavior / drug effects*
  • Feeding Behavior / physiology
  • Feeding Behavior / psychology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / physiology
  • Rimonabant / pharmacology*
  • Sucrose / administration & dosage*

Substances

  • Cannabinoid Receptor Antagonists
  • Receptor, Cannabinoid, CB1
  • Sucrose
  • Dronabinol
  • HU 211
  • Rimonabant