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Varenicline modulates ethanol and saccharin consumption in adolescent male and female C57BL/6J mice.

ABSTRACT: Adolescence is a critical period in brain development that coincides with the initiation of alcohol use. Nicotinic acetylcholine receptors (nAChR) have been shown to modulate ethanol behaviors in adult humans and in animal models; however, the role of these receptors in adolescent ethanol behaviors has not been explored. Throughout adolescence, nAChR expression undergoes large-scale developmental changes which may alter behavioral responses to ethanol. Here we examined the effect of varenicline, a nAChR partial agonist, on ethanol consumption, ataxia, sedation, and metabolism in adolescent male and female C57BL/6J mice. The effect of varenicline on ethanol consumption was tested through the Drinking-in-the-Dark (DID) paradigm that models binge-like ethanol consumption. To ensure that results were specific for ethanol, we also tested the effect of varenicline on saccharin consumption. Additionally, varenicline was administered 30min prior to an acute injection of ethanol before being tested for ataxia on the balance beam, sedation using the loss of righting reflex, or ethanol metabolism. Varenicline dose dependently decreased ethanol consumption, but also influenced saccharin intake. Varenicline showed no significant effect on ethanol metabolism, ataxia, or sedation. Unlike its effects in adult animals, varenicline is able to reduce ethanol consumption without increasing the ataxic and sedative effects of ethanol. This work suggests that the neurobiological mechanisms of ethanol behaviors may change across the lifespan and highlights the need for more research on the role of nAChRs in ethanol behaviors throughout development.

SUBMITTER: Kamens HM

PROVIDER: S-EPMC5794646 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Varenicline modulates ethanol and saccharin consumption in adolescent male and female C57BL/6J mice.

Kamens Helen M HM Silva Constanza C Peck Colette C Miller Carley N CN

Brain research bulletin 20170801

Adolescence is a critical period in brain development that coincides with the initiation of alcohol use. Nicotinic acetylcholine receptors (nAChR) have been shown to modulate ethanol behaviors in adult humans and in animal models; however, the role of these receptors in adolescent ethanol behaviors has not been explored. Throughout adolescence, nAChR expression undergoes large-scale developmental changes which may alter behavioral responses to ethanol. Here we examined the effect of varenicline, ...[more]

PMID: 28778837

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Project description:BackgroundIn recent years, much attention has been given to the lack of reproducibility in biomedical research, particularly in preclinical animal studies. This is a problem that also plagues the alcohol research field, particularly in consistent consumption in animal models of alcohol use disorders. One often overlooked factor that could affect reproducibility is the maintenance diet used in preclinical studies.MethodsHerein, 2 well-established models of alcohol consumption, the "drinking in the dark" (DID) procedure and the continuous 2-bottle choice (C2BC) paradigm, were employed to determine the effects of diet on ethanol (EtOH) consumption. Male C57BL/6J mice were given 1 of 6 standard rodent chow diets obtained from Purina LabDiet(®) , Inc. (Prolab(®) RMH 3000) or Harlan(®) Laboratories, Inc. (Teklad Diets T.2916, T.2918, T.2920X, T.7912, or T.8940). A separate group of animals were used to test dietary effects on EtOH pharmacokinetics and behavioral measures following intraperitoneal (IP) injections of various doses of EtOH.ResultsMice eating Harlan diets T.2916 (H2916) and T.2920X (H2920) consumed significantly less EtOH and exhibited lower blood EtOH concentrations (BECs) during DID; however, during C2BC, animals maintained on Harlan T.7912 (H7912) consumed more EtOH and had a higher EtOH preference than the other diet groups. EtOH consumption levels did not stem from changes in alcohol pharmacokinetics, as a separate group of animals administered EtOH IP showed no difference in BECs. However, animals on Harlan diet T.2920X (H2920) were more sensitive to alcohol-induced locomotor activity in an open-field task. No diet-dependent differences were seen in alcohol-induced sedation as measured with loss of righting reflex.ConclusionsAlthough these data do not identify a specific mechanism, together, they clearly show that the maintenance diet impacts EtOH consumption. It is incumbent upon the research community to consider the importance of describing nutritional information in methods, which may help decrease interlaboratory reproducibility issues.

Dataset Information

Varenicline modulates ethanol and saccharin consumption in adolescent male and female C57BL/6J mice.

Publications

Varenicline modulates ethanol and saccharin consumption in adolescent male and female C57BL/6J mice.

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