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

Kamens, Helen M.; Silva, Constanza; Peck, Colette; Miller, Carley N.

doi:10.1016/j.brainresbull.2017.07.020

Cited by 17 publications

(16 citation statements)

References 48 publications

(94 reference statements)

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“…This intake was significantly higher than what has been previously reported with other DID experiments that used lower concentrations. Using 0.1% saccharin, Zhou et al (2019) found intakes around 0.1 g/kg in 4 h (male B6), while Kamens et al (2018) showed drinking up to ∼0.02 g/kg in 2 h (adolescent male and female B6; 0.033% saccharin). Our animals preferred the concentration of 1.06%.…”

Section: ! 12mentioning

confidence: 99%

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

Morales

Rodríguez-Borillo

Font

et al. 2020

Behavioural Pharmacology

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Chronic alcohol (EtOH) binging has been associated with long-term neural adaptations that lead to the development of addiction. Many of the neurobiological features of EtOH abuse are shared with other forms of binging, like pathological feeding. The drinkingin-the-dark paradigm (DID) has been used extensively to study the neurobiology of EtOH binge-like drinking due to its ability to promote high intakes relevant to human behavior. DID can also generate high consumption of other tastants, but this procedure has not been fully adapted to study forms of binging behavior that are not alcohol-driven. In the present study we used a modified version of DID that uses multiple bottle availability to promote even higher levels of EtOH drinking in male C57BL/6J mice and allows a thorough investigation of tastant preferences. We assessed whether administration of systemic naltrexone (NTX) could reduce binging on EtOH, sucrose, and saccharin separately as well as in combination. Our multiple bottle DID procedure resulted in heightened levels of consumption compared to previously reported data using this task. We found that administration of the opioid receptor antagonist NTX reduced intakes of preferred, highly concentrated EtOH, sucrose, and saccharin. We also report that NTX was able to reduce overall intakes when animals were allowed to self-administer EtOH, sucrose, or saccharin in combination. Our modified DID procedure provides a novel approach to study binging behavior that extends beyond EtOH to other tastants (i.e., sucrose and artificial sweeteners), and has implications for the study of the neuropharmacology of binge drinking.

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Section: ! 12mentioning

confidence: 99%

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

Morales

Rodríguez-Borillo

Font

et al. 2020

Behavioural Pharmacology

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“…Additionally, previous clinical research suggests that there are sex differences in the efficacy of varenicline, with efficacy being greater in females (McKee et al, 2016). However, previous research with mice shows that there are no sex differences in the effects of varenicline on EtOH drinking (Kamens et al, 2018). Clinical research with naltrexone has also indicated differences in effects for men and women, but overall efficacy appears similar for both sexes (Baros et al, 2008).…”

Section: Discussionmentioning

confidence: 93%

An improved model of ethanol and nicotine co-use in female P rats: Effects of naltrexone, varenicline, and the selective nicotinic α6β2* antagonist r-bPiDI

Maggio

Saunders

Nixon

et al. 2018

Drug and Alcohol Dependence

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Background: Although pharmacotherapies are available for alcohol (EtOH) or tobacco use disorders individually, it may be possible to develop a single pharmacotherapy to treat heavy drinking tobacco smokers by capitalizing on the commonalities in their mechanisms of action. Methods: Female alcohol-preferring (P) rats were trained for EtOH drinking and nicotine self-administration in two phases: (1) EtOH alone (0 vs. 15% EtOH, 2-bottle choice) and (2) concomitant access, during which EtOH access continued with access to nicotine (0.03 mg/kg/infusion, i.v.) using a 2-lever choice procedure (active vs. inactive lever) in which the fixed ratio (FR) requirement was gradually increased to FR30. When stable co-use was obtained, rats were pretreated with varying doses of naltrexone, varenicline, or r-bPiDI, an α6β2* subtype-selective nicotinic acetylcholine receptor antagonist shown previously to reduce nicotine self-administration. Results: While EtOH intake was initially suppressed in phase 2 (co-use), pharmacologically relevant intake for both substances was achieved by raising the “price” of nicotine to FR30. In phase 2, naltrexone decreased EtOH and water consumption but not nicotine intake; in contrast, naltrexone in phase 1 (EtOH only) did not significantly alter EtOH intake. Varenicline and r-bPiDI in phase 2 both decreased nicotine self-administration and inactive lever pressing, but neither altered EtOH or water consumption. Conclusions: These results indicate that increasing the “price” of nicotine increases EtOH intake during co-use. Additionally, the efficacy of naltrexone, varenicline, and r-bPiDI was specific to either EtOH or nicotine, with no efficacy for co-use. Nevertheless, future studies on combining these treatments may reveal synergistic efficacy.

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“…Both mecamylamine and nicotine reduce binge DID consumption in male mice 7 . Varenicline has been shown to reduce binge consumption in both male and female C57BL/6J mice 29,30 . Moreover, varenicline requires the α4 nAChR subunit to reduce alcohol consumption, as it does not reduce alcohol consumption in male α4 KO mice 29 .…”

Section: Discussionmentioning

confidence: 99%

Enhancement of alcohol aversion by the nicotinic acetylcholine receptor drug sazetidine‐A

et al. 2020

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The prevalence of alcohol use disorders (AUDs) has steadily increased in the United States over the last 30 years. Alcohol acts on multiple receptor systems including the nicotinic acetylcholine receptors (nAChRs), which are known to mediate alcohol consumption and reward. We previously reported that the preclinical drug sazetidine‐A, a nAChR agonist and desensitizer, reduces alcohol consumption without affecting nicotine consumption in C57BL/6J mice. Here, we found that sazetidine‐A enhances the expression of alcohol aversion without affecting the expression or acquisition of conditioned alcohol reward in C57BL/6J mice. Microinjection of sazetidine‐A into the ventral midbrain targeting the ventral tegmental area (VTA) reduced binge alcohol consumption, implicating this region in mediating the effects of sazetidine‐A. Furthermore, the sazetidine‐A‐induced reduction in alcohol consumption was mediated by non‐α4 containing nAChRs, as sazetidine‐A reduced binge alcohol consumption in both α4 knock‐out and wild‐type mice. Finally, we found that in mice pretreated with sazetidine‐A, alcohol induced Fos transcript in Th‐, but not Gad2‐expressing neurons in the VTA as measured by increased Fos transcript expression. In summary, we find that sazetidine‐A enhances the expression of alcohol aversion, which may underlie the reduction in alcohol consumption induced by sazetidine‐A. Elucidating the identity of non‐α4 nAChRs in alcohol aversion mechanisms will provide a better understanding the complex role of nAChRs in alcohol addiction and potentially reveal novel drug targets to treat AUDs.

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

Cited by 17 publications

References 48 publications

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

Effects of naltrexone on alcohol, sucrose, and saccharin binge-like drinking in C57BL/6J mice: a study with a multiple bottle choice procedure

An improved model of ethanol and nicotine co-use in female P rats: Effects of naltrexone, varenicline, and the selective nicotinic α6β2* antagonist r-bPiDI

Enhancement of alcohol aversion by the nicotinic acetylcholine receptor drug sazetidine‐A

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