Effect of Aripiprazole on Anxiety Associated With Ethanol Physical Dependence and on Ethanol-Induced Place Preference

Abstract

Abstract. In the present study, we investigated the effect of aripiprazole, a dopamine system stabilizer, on ethanol-induced psychological and physiological dependence and anxiety-like behavior. First we determined the effect of aripiprazole, a dopamine system stabilizer, on the development and expression of ethanol-induced place preference. Both the development and expression of ethanol-induced place preference was significantly suppressed by treatment of aripiprazole. Next, the withdrawal score gradually increased with increasing duration after the withdrawal from ethanol for 6 days in vehicle-treated mice and the maximal score was observed 10 h after the ethanol withdrawal. Aripiprazole caused no changes in the withdrawal score as compared to vehicletreated mice. Under these conditions we investigated the effect of aripiprazole on the anxiety-like behavior of ethanol physical dependent mice, which were animals subjected to ethanol vapor for 6 days. The significant decrease of time spent in the open arms and number of open arm entries characterize the anxiety-like behavior in ethanol physical dependent mice, compared to control mice. These decreases were reversed by treatment of aripiprazole, which were inhibited by WAY100635, a serotonin 5-HT 1A receptor antagonist. The present findings suggest that aripiprazole was efficient for reversing ethanol-induced place preference and anxiety-like behavior.

Ameliorating effects of aripiprazole on cognitive functions and depressive-like behavior in a genetic rat model of absence epilepsy and mild-depression comorbidity

“…Relative to the anxiety models and therefore, the possible anxiolytic properties of APZ, it is worth noting that in the experiments by Shibasaki et al (2012), APZ alone reduced the time spent in the open arms in the elevated plus maze in control animals; whereas it reversed the anxiety-like behavior in ethanol physically dependent mice. This latter result is in line with what is observed in the WAG/Rij rat, however, this strain is not considered to have an elevated anxiety in comparison to control animals .…”

“…Other results obtained in the two-compartment exploratory test showed that APZ improves spatial memory in rats and has antidepressant and anxiolytic effects (Bourin et al, 2009;Burda et al, 2011). It has also been showed that APZ ameliorate phencyclidine-induced impairment of recognition memory through dopamine D 1 and serotonin 5-HT 1A receptors (Nagai et al, 2009) and anxiety-like behavior in ethanol physical dependent mice (Shibasaki et al, 2012). However, it has also been demonstrated that both firstand second-generation antipsychotic medications can lower seizure threshold, increasing the chances of seizure induction (Hedges et al, 2003).…”

CRF1receptor-dependent increases in irritability-like behavior during abstinence from chronic intermittent ethanol vapor exposure

“…The motivational symptoms of withdrawal have been found to last much longer (> 2 weeks) into protracted abstinence. Increases in anxiety-like behavior in the elevated plus maze and depressive-like behavior (e.g., immobility) in the forced swim test have been reported in ethanol-dependent rats and mice during acute withdrawal from ethanol vapor and after protracted abstinence (Kallupi et al, 2014, Valdez et al, 2002b, Zhao et al, 2007, Williams et al, 2012, Marcinkiewcz et al, 2015, Shibasaki et al, 2012, Walker et al, 2010). Impairments in brain reward function, reflected by elevations of intracranial self-stimulation (ICSS) thresholds, have also been observed during acute withdrawal from ethanol vapor in dependent rats (Schulteis et al, 1995).…”

Dopamine and Alcohol Dependence: From Bench to Clinic

“…Furthermore, repeated systemic aripiprazole administration decreases alcohol intake in alcohol-preferring rats [180], while single oral administration dose-dependently decreases alcohol self-administration in outbred rats [181]. In addition, aripiprazole has been shown to reverse alcohol-induced place preference and anxiety-like behaviour in mice [182].…”