Selective breeding for high alcohol preference is associated with increased sensitivity to cannabinoid reward within the nucleus accumbens shell

Abstract

Rationale: The rate of cannabinoid intake by those with alcohol use disorder (AUD) exceeds that of the general public. The high prevalence of co-abuse of alcohol and cannabis has been postulated to be predicated upon both a common predisposing genetic factor and the interaction of the drugs within the organism. The current experiments examined the effects of cannabinoids in an animal model of AUD.

Objectives: The present study assessed the reinforcing properties of a cannabinoid receptor 1 (CB1) agonist self-administered directly into the nucleus accumbens shell (AcbSh) in female Wistar and alcohol-preferring (P) rats.

Methods: Following guide cannulae surgery aimed at AcbSh, subjects were placed in an operant box equipped with an 'active lever' (fixed ratio 1; FR1) that caused the delivery of the infusate and an 'inactive lever' that did not. Subjects were arbitrarily assigned to one of seven groups that self-administered either artificial cerebrospinal fluid (aCSF), or 3.125, 6.25, 12.5, or 25 pmol/100 nl of O-1057, a water-soluble CB1 agonist, dissolved in aCSF. The first four sessions of acquisition are followed by aCSF only infusates in sessions 5 and 6 during extinction, and finally the acquisition dose of infusate during session 7 as reinstatement.

Results: The CB1 agonist was self-administered directly into the AcbSh. P rats self-administered the CB1 agonist at lower concentrations and at higher rates compared to Wistar rats.

Conclusions: Overall, the data indicate selective breeding for high alcohol preference has produced rats divergent in response to cannabinoids within the brain reward pathway. The data support the hypothesis that there can be common genetic factors influencing drug addiction.

Keywords: Alcohol-preferring; Cannabinoid; Intracranial self-administration; Nucleus accumbens shell; Reinforcement; Reward.