Sex differences in the development of conditioned place preference induced by intragastric alcohol administration in mice

• Published in: Drug and alcohol dependence Vol. 229; no. Pt A; p. 109105
• Main Authors: Barros-Santos, Thaísa, Libarino-Santos, Matheus, Anjos-Santos, Alexia, Lins, Juliana F., Leite, João P.C., Pacheco, Roseliz C., Nascimento-Rocha, Victor, Kisaki, Natali D., Tamura, Eduardo K., Oliveira-Lima, Alexandre J., Berro, Laís F., Uetanabaro, Ana Paula T., Nicoli, Jacques R., Marinho, Eduardo A.V.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2021; Elsevier Science Ltd
• Subjects: Alcohol; Alcohol use; Alcohols; Animals; Conditioned place preference; Conditioning; Conditioning, Classical; Dosage; Dose-Response Relationship, Drug; Drinking behavior; Efficacy; Ethanol; Female; Females; Gender aspects; Gender differences; Induced; Intragastric; Male; Males; Management; Mice; Place preference conditioning; Reward; Rodents; Sex Characteristics; Sex differences; Intragastric; Alcohol; Male; Female; Mice; Conditioned place preference
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/j.drugalcdep.2021.109105

The present study aimed to identify for the first time sex differences in the development of CPP induced by intragastric alcohol administration in mice. Male and female adult Swiss mice were submitted to 16 days of conditioning with alcohol (0.5–3.0 g/kg, N = 8/dose/sex), with 2 post-conditioning tests (after 8 and 16 sessions) during the protocol. 8 days of conditioning (4 alcohol sessions, 4 saline sessions) with intragastric alcohol administration were sufficient to induce CPP in male mice at the doses of 1.0, 1.5 and 2.0 g/kg. However, only higher doses (2.0, 2.5 and 3.0 g/kg) induced CPP in female mice using an 8-day conditioning protocol, while a 16-day conditioning protocol was necessary for the development of intragastric alcohol-induced CPP at the doses of 1.0 and 1.5 g/kg. Regardless of the conditioning protocol, higher doses or alcohol that had rewarding effects in females (2.5 and 3.0 g/kg) did not induce CPP in males, with a significant difference between males and females at those doses. Analysis of the potency (EC50) and efficacy (Emax) of alcohol in inducing CPP when administered intragastrically in male and female mice showed significant sex differences with 8 conditioning sessions. Our data show a clear protocol (8 vs 16 days) and dose difference between male and female Swiss mice regarding the development of CPP induced by intragastric alcohol administration. Intragastric alcohol administration is closer to human drinking, and our protocol provides a more translational approach to studying the rewarding effects of alcohol in mice. •Mice develop conditioned place preference (CPP) to intragastric (i.g.) alcohol.•8 conditioning days with i.g. alcohol induced CPP in male mice at low doses.•Higher doses of i.g. alcohol were needed to induce CPP in female mice in 8 days.•Higher doses that induced CPP in females did not induce CPP in males.•Sex differences were observed for the potency and efficacy of alcohol-induced CPP.