Nucleus accumbens lentiviral-mediated gain of function of the oxytocin receptor regulates anxiety- and ethanol-related behaviors in adult mice

Bahí, Amine; Mansouri, Shamma Al; Maamari, Elyazia Al

doi:10.1016/j.physbeh.2016.06.009

Cited by 36 publications

(26 citation statements)

References 79 publications

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“…In contrast, reduced activity produced by a high oxytocin dose (3 mg/kg) did not recover to control levels until at least 40–45 min into the test session. These results are congruent with other reports indicating that low-dose anxiolytic effects of oxytocin can be distinguishd from sedative effects produced by higher doses of the neuropeptide (Bahi et al, 2016; Klenerova et al, 2009). Interestingly, central (icv.)…”

Section: Discussionsupporting

confidence: 92%

“…Few studies have examined the role of oxytocin receptors in mediating the neuropeptide’s effects on motivational actions of alcohol. Recent studies involving viral-mediated overexpression of oxytocin receptors in the nucleus accumbens core have implicated a role for these receptors in ethanol drinking and conditioned reward (Bahi, 2015; Bahi et al, 2016). However, it is noteworthy that oxytocin was shown to block ethanol-induced ataxic and sedative/hypnotic effects via an apparent direct interaction with delta-subunit containing GABA-A receptors (Bowen et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…For example, direct (intracerebroventricular) infusion of oxytocin blocked alcohol-induced increases in dopamine release in the nucleus accumbens and reduced voluntary alcohol consumption in Wistar rats (Peters et al, 2016). Additionally, viral-mediated overexpression of oxytocin receptors in the nucleus accumbens reduced alcohol-induced conditioned place preference and alcohol consumption in C57BL/6J mice (Bahi, 2015; Bahi et al, 2016). Taken together, accumulating evidence suggests that the oxytocin system may represent a promising target for the treatment of alcohol use disorders (Lee et al, 2016; Lee and Weerts, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Oxytocin Reduces Ethanol Self‐Administration in Mice

King

Griffin

Luderman

et al. 2017

Alcoholism Clin & Exp Res

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Background Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. Methods Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking (“drinking-in-the-dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, ethanol (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive- ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Results Oxytocin (0, 0.3, 1, 3 or 10mg/kg) dose-dependently reduced ethanol consumption (maximal 45% reducton) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin’s effect was blocked by pretreatment with an oxytocin receptor antagonist and the pattern of contacts (licks) at the ethanol bottle suggested a reduction in motivation to drink ethanol. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for ethanol and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for ethanol at doses that did not alter responding for sucrose. Discussion These results indicate that oxytocin reduces ethanol consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for ethanol at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Neverthess, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxytocin Reduces Ethanol Self‐Administration in Mice

King

Griffin

Luderman

et al. 2017

Alcoholism Clin & Exp Res

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“…Elevated plus maze test As described previously, we used a standard EPM assay to assess anxiety-like behavior (Bahi 2016;Bahi et al 2016). In brief, the apparatus consisted of two open arms (OA) (50 × 10 cm 2 ) and two enclosed arms (CA) (50 × 10 × 40 cm 3 ), which were connected by a central platform (10 × 10 cm 2 ).…”

Section: Anxiety-and Ethanol-related Behavior Testsmentioning

confidence: 99%

“…Open field (OF) test Spontaneous and exploratory locomotor activity and anxiety were tested in an OF test as reported in our previous studies (Bahi 2016;Bahi et al 2016). In brief.…”

Section: Anxiety-and Ethanol-related Behavior Testsmentioning

confidence: 99%

Viral-mediated overexpression of the Myelin Transcription Factor 1 (MyT1) in the dentate gyrus attenuates anxiety- and ethanol-related behaviors in rats

Bahí

Dreyer

2017

Psychopharmacology

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Rationale Myelin Transcription Factor 1 (MyT1), a member of the Zinc Finger gene family, plays a fundamental role in the nervous system. Recent research has suggested that this transcription factor is associated with the pathophysiology of psychiatric disorders including addiction, schizophrenia, and depression. However, the role of MyT1 in anxiety-and ethanolrelated behaviors is still unknown. Objectives We evaluated the effects of lentiviral-mediated overexpression of MyT1 in the dentate gyrus (DG) on anxiety-and ethanol-related behaviors in rats. Methods We used the elevated plus maze (EPM) and the open field (OF) tests to assess anxiety-like behavior and a twobottle choice procedure to measure the effects of MyT1 on ethanol intake and preference. Results MyT1 overexpression produced anxiolytic-like effects in the EPM test and decreased the number of fecal boli in the OF test, without affecting locomotor activity in both behavioral tests. Next, we demonstrated that ethanol intake and preference were decreased in the MyT1-overexpressing rats with no effect on saccharin and quinine, used to assess taste discrimination, and no effect on ethanol clearance suggesting specific alterations in the rewarding effects of ethanol.Most importantly, ectopic MyT1 overexpression increased both MyT1 and BDNF mRNA levels in the DG. Using Pearson's correlation, results showed a strong negative relationship between MyT1 mRNA and anxiety parameters and ethanol consumption and a positive correlation between MyT1 and BDNF mRNAs. Conclusion Taken together, MyT1 along with being a key component in anxiety may be a suitable candidate in the search of the molecular underpinnings of alcoholism.

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