Operant, oral alcohol self-administration: Sex differences in Sardinian alcohol-preferring rats

Irene Lorrai; Andrea Contini; Gian Luigi Gessa; Claudia Mugnaini; Federico Corelli; Giancarlo Colombo; Paola Maccioni

doi:10.1016/j.alcohol.2019.04.003

Operant, oral alcohol self-administration: Sex differences in Sardinian alcohol-preferring rats

Alcohol. 2019 Sep:79:147-162. doi: 10.1016/j.alcohol.2019.04.003. Epub 2019 Apr 26.

Authors

Irene Lorrai¹, Andrea Contini², Gian Luigi Gessa¹, Claudia Mugnaini³, Federico Corelli³, Giancarlo Colombo⁴, Paola Maccioni⁵

Affiliations

¹ Neuroscience Institute, Section of Cagliari, National Research Council of Italy, I-09042, Monserrato (CA), Italy; Department of Biomedical Sciences, University of Cagliari, I-09042, Monserrato (CA), Italy.
² Department of Biomedical Sciences, University of Sassari, I-07100, Sassari (SS), Italy.
³ Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, I-53100, Siena (SI), Italy.
⁴ Neuroscience Institute, Section of Cagliari, National Research Council of Italy, I-09042, Monserrato (CA), Italy. Electronic address: colomb@unica.it.
⁵ Neuroscience Institute, Section of Cagliari, National Research Council of Italy, I-09042, Monserrato (CA), Italy.

PMID: 31029630
DOI: 10.1016/j.alcohol.2019.04.003

Abstract

Sardinian alcohol-preferring (sP) rats have been selectively bred, over almost 40 years, for high alcohol preference and consumption. sP rats have served as an animal model for more than 120 published studies. With very few exceptions, however, these studies have always employed male sP rats, and little is known about alcohol-related behaviors in female sP rats. The present study was designed to fill, at least in part, this gap. Accordingly, alcohol self-administration under the fixed ratio 4 schedule of reinforcement was compared among male, intact female, and ovariectomized female sP rats. Additionally, it was investigated whether i) estrous cycle influenced alcohol self-administration, and ii) alcohol self-administration in the three sP rat groups differed in sensitivity to pharmacological manipulation. Lever-responding for alcohol was steadily higher in male than intact and ovariectomized female sP rats; conversely, because of large sex differences in rat body weight, estimated amount of self-administered alcohol (in g/kg) did not differ among the three sP rat groups or occasionally was higher in intact female than male and ovariectomized female sP rats. Blood alcohol levels derived from self-administered alcohol i) did not differ among the three sP rat groups and ii) were positively correlated with the number of lever-responses for alcohol and the estimated amount of self-administered alcohol. Treatment with the opioid receptor antagonist, naloxone (0, 0.3, 1, and 3 mg/kg, i.p. [intraperitoneally]), and the positive allosteric modulator of the GABA_B receptor, GS39783 (0, 25, 50, and 100 mg/kg, i.g. [intragastrically]), reduced alcohol self-administration with comparable potency and efficacy in the three sP rat groups. The impact of the estrous cycle on alcohol self-administration was relatively modest, limited to a tendency toward a reduction in the number of lever-responses for alcohol and the estimated amount of self-administered alcohol in estrus and metestrus. Together, these results provide the first characterization of alcohol-seeking and -taking behavior in female sP rats.

Keywords: Alcohol drinking; Alcohol self-administration; Estrous cycle; GS39783; Male and female Sardinian alcohol-preferring (sP) rats; Naloxone.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Alcohol Drinking*
Animals
Blood Alcohol Content
Conditioning, Operant*
Cyclopentanes / pharmacology
Drug Tolerance
Estrous Cycle
Female
Male
Naloxone / pharmacology
Pyrimidines / pharmacology
Rats
Self Administration*
Sex Characteristics*

Substances

Blood Alcohol Content
Cyclopentanes
N,N'-dicyclopentyl-2-methylsulfanyl-5-nitro-pyrimidine-4,6-diamine
Pyrimidines
Naloxone