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

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2020-10, Vol.197, p.173002-173002, Article 173002
• Main Authors: Hauser, Sheketha R., Katner, Simon N., Waeiss, Robert A., Truitt, William A., Bell, Richard L., McBride, William J., Rodd, Zachary A.
• Format: Article
• Language: English
• Subjects: Alcohol-preferring; Alcoholism - complications; Alcoholism - genetics; Animals; Cannabinoid; Cannabinoids - administration & dosage; Cannabinoids - pharmacology; Conditioning, Operant - drug effects; Disease Models, Animal; Ethanol - administration & dosage; Ethanol - pharmacology; Female; Intracranial self-administration; Marijuana Abuse - complications; Nucleus Accumbens - drug effects; Nucleus accumbens shell; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - agonists; Reinforcement; Reinforcement, Psychology; Reward; Selective Breeding; Self Administration
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2020.173002

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. 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. 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. 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. 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. •O-1057, a CB1 agonist, is self-administered directly into the AcbSh of female rats.•P rats self-administered O-1057 at lower concentrations compared to Wistar rats.•P rats received more self-infusions of O-1057 than Wistar rats.•Alcohol preference may enhance sensitivity to the rewarding effects of cannabinoids.