Effects of Aripiprazole, an Atypical Antipsychotic, on the Motor Alterations Induced by Acute Ethanol Administration in Mice

Viana, Thércia Guedes; Almeida-Santos, Ana Flávia; Aguiar, Daniele C.; Moreira, Fabrício A.

doi:10.1111/bcpt.12036

Cited by 27 publications

(12 citation statements)

References 51 publications

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“…An automated tracking system (Any-Maze) was used to track the locomotion of each subject in an open, plexiglass box (25 cm × 25 cm × 25 cm) that was evenly illuminated. Locomotion was defined as the distance travelled (cm) during the 10 minute trial (Viana et al 2013). …”

Section: Methodsmentioning

confidence: 99%

Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice

et al. 2017

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Background Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. Methods In this study, we treated young (2–3 months old) and aged (22–24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects. In addition, we pretreated separate groups of young and aged mice with histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275) and then administered HAL. Results Our results show that the motor side effects of HAL are exaggerated in aged mice as compared to young mice and that HDAC inhibitors are able to reverse the severity of these deficits. HAL-induced motor deficits in aged mice are associated with an age- and drug-dependent decrease in striatal D2R protein levels and functionality. Further, histone acetylation was reduced while histone trimethylation was increased at specific lysine residues of H3 and H4 within the Drd2 promoter in the striatum of aged mice. HDAC inhibitors, particularly VPA, restored striatal D2R protein levels and functionality and reversed age- and drug-related histone modifications at the Drd2 promoter. Conclusions These results suggest that epigenetic changes at the striatal Drd2 promoter drive age-related increases in antipsychotic side effect susceptibility, and HDAC inhibitors may be an effective adjunct treatment strategy to reduce side effects in aged populations.

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Section: Methodsmentioning

confidence: 99%

Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice

et al. 2017

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“…In line with the hypothesis that a partial dopamine D2 agonist would block the reinforcing effects of alcohol, aripiprazole attenuates alcohol's ability to increase the locomotor activity in mice [178,179](an indirect measure of activation of the mesolimbic dopamine system). On the other hand, aripiprazole did not interfere with the alcohol-induced impairment in motor balance as measured by rotarod test [179].…”

Section: Preclinical Evidence For the Use Of Partial Dopamine Agonistmentioning

confidence: 65%

“…On the other hand, aripiprazole did not interfere with the alcohol-induced impairment in motor balance as measured by rotarod test [179]. 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].…”

Section: Preclinical Evidence For the Use Of Partial Dopamine Agonistmentioning

confidence: 83%

Dopamine and Alcohol Dependence: From Bench to Clinic

Jayaram‐Lindström¹,

Ericson²,

Steensland³

et al. 2016

Recent Advances in Drug Addiction Research and Clinical Applications

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Alcohol dependence, a chronic relapsing psychiatric disorder, is a major cause of mortality and morbidity. The role of dopamine in alcohol-induced reward as well in the development of alcohol dependence is reviewed herein. Both preclinical and clinical studies have suggested that alcohol activates the mesolimbic dopamine system (defined as a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc, i.e. ventral striatum)) leading to a euphoric sensation. Alcohol dependence is characterized by a disruption in the reward-related brain areas including fewer dopamine D2 receptors in ventral striatum. Investigations of the underlying dopaminergic mechanisms involved during the development and maintenance of alcohol dependence could identify novel targets. Human and rodent experimental studies show that dopamine receptor antagonists, agonists and partial agonists as well as dopamine stabilizers influencing dopamine transmission, alter alcohol-mediated behaviours and thus may be potential treatment targets for alcohol dependence. Although there exists promising preclinical results, the majority of placebo-controlled randomized clinical trials with traditional dopamine antagonists and agonists have so far have been discouraging. Furthermore, the severe side-effect profiles of many of these compounds may limit their clinical use. Newer dopamine agents, such as partial agonists and dopamine stabilizers, attenuate alcohol-mediated behaviours in rodents as well as humans. Preclinical as well as clinical studies have shown that substances indirectly targeting the mesolimbic dopamine system may be potential targets for attenuation of alcohol reward. Collectively, the data reviewed herein may contribute to further understanding the complex mechanisms involved in development of alcohol dependence and we suggest that the newer dopamine agents as well as indirect modulators of dopamine signalling deserve to be further evaluated for treatment of alcohol dependence.

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“…Aripiprazole was injected 60 min before PTZ or electroshock (ECT). The doses of drugs were chosen based on previously published studies and pilot experiments [18,19,20,21]. All injections and tests were conducted between 9:00 a.m. and 3:00 p.m. …”

Section: Methodsmentioning

confidence: 99%

The Effects of Sub-Chronic Treatment with Aripiprazole on Pentylenetetrazole- and Electroshock-Induced Seizures in Mice: The Role of Nitric Oxide

et al. 2015

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Almost all antipsychotics have been associated with a risk of epileptic seizure provocation. Aripiprazole is a novel atypical antipsychotic. The risk of seizures with aripiprazole is reported to be the lowest among atypical agents. In this study, we investigated the effect of aripiprazole on seizure of mice in sub-chronic treatments. We also examined the interaction of nitric oxide (NO) with aripiprazole in seizure experiments. Mice received aripiprazole for 6 days and then on the 7th day aripiprazole was injected 60 min before intraperitoneal pentylenetetrazole or electroshock. L-NAME (non-selective NO synthase (NOS) inhibitor), 7-nitroindazole (neuronal NOS selective inhibitor), aminoguanidine (inducible NOS selective inhibitors) or L-arginine (NO donor), all were injected 5 min before aripiprazole in separate groups. The results of both seizure models demonstrated anti-epileptic properties of aripiprazole in sub-chronic administrations. Co-administration of aripiprazole and selective and non-selective NOS inhibitors prevented the anticonvulsant effect of aripiprazole. While L-arginine and aripiprazole co-administration increased the clonic seizure threshold and protection against tonic seizure and death, these effects were not significant. The current results indicated that aripiprazole has anticonvulsant effects probably through the release of NO.

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Effects of Aripiprazole, an Atypical Antipsychotic, on the Motor Alterations Induced by Acute Ethanol Administration in Mice

Cited by 27 publications

References 51 publications

Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice

Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice

Dopamine and Alcohol Dependence: From Bench to Clinic

The Effects of Sub-Chronic Treatment with Aripiprazole on Pentylenetetrazole- and Electroshock-Induced Seizures in Mice: The Role of Nitric Oxide

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