The Monoamine Stabilizer (-)-OSU6162 Attenuates Voluntary Ethanol Intake and Ethanol-Induced Dopamine Output in Nucleus Accumbens

Steensland, Pia; Fredriksson, Ida; Holst, Sarah; Feltmann, Kristin; Franck, Johan; Schilström, Björn; Carlsson, Arvid

doi:10.1016/j.biopsych.2012.06.018

Cited by 58 publications

(82 citation statements)

References 54 publications

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“…Using the modified intermittent access paradigm with three consecutive days of access to 20% alcohol for seven weeks, the median alcohol intake during the last week of access in all alcohol-drinking animals was 3.2 g/kg (1.8-5.8 g/kg) and the preference was 36.4% (16.0-46.2%). This is in agreement with previous studies using intermittent access paradigms in which alcohol consumption up to 6 g/kg has been described [22,[29][30][31][32] and higher compared to studies in which Wistar rats were given continuous alcohol access [20,31,33]. Moreover, compared to our recent study [16] in which the animals had intermittent access to 20% alcohol on Mondays, Wednesdays and Fridays the modified model used herein resulted in a higher alcohol intake and a higher preference as well as an increased intake and preference over time.…”

Section: Alcohol Intake Using Three Consecutive Days Of Intermittent supporting

confidence: 93%

“…A large individual variation in alcohol intake was found among all alcohol-drinking animals, which enabled subgrouping of animals with high, intermediate and low alcohol intake. This finding is in line with previous studies [22,32]. Since one part of this study is devoted to the introduction of and the characterization of alcohol intake using the modified intermittent access paradigm the ID group is shown in the figures despite being excluded in the statistical analysis, since the behavioral analysis was focused on the most extreme subgroups.…”

Section: Alcohol Intake Using Three Consecutive Days Of Intermittent supporting

confidence: 91%

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Subgroup-dependent effects of voluntary alcohol intake on behavioral profiles in outbred Wistar rats

Momeni

Roman

2014

Behavioural Brain Research

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Experimental animal models are critical for understanding the genetic, environmental and neurobiological underpinnings of alcohol use disorders. Limited studies investigate alcohol-induced effects on behavior using free-choice paradigms. The aims of the present experiment were to study voluntary alcohol intake using a modified intermittent access paradigm, investigate the effects of voluntary alcohol intake on behavioral profiles in water- and alcohol-drinking rats, and select extreme low- and high-drinking animals for a more detailed behavioral characterization. Sixty outbred male Wistar rats were randomized into water and alcohol groups. Behavioral profiles in the multivariate concentric square field™ (MCSF) test were assessed prior to and after voluntary alcohol intake. The animals had intermittent access to 20% alcohol and water for three consecutive days per week for seven weeks. The results revealed increased alcohol intake over time. No major alcohol-induced differences on behavior profiles were found when comparing water- and alcohol-drinking animals. The high-drinking animals displayed an alcohol deprivation effect, which was not found in the low-drinking animals. High-drinking rats had lower risk-taking behavior prior to alcohol access and lower anxiety-like behavior after voluntary alcohol intake compared to low-drinking rats. In conclusion, the modified intermittent access paradigm may be useful for pharmacological manipulation of alcohol intake. With regard to behavior, the present findings highlights the importance of studying subgroup-dependent differences and add to the complexity of individual differences in behavioral traits of relevance to the vulnerability for excessive alcohol intake.

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Section: Alcohol Intake Using Three Consecutive Days Of Intermittent supporting

confidence: 93%

Section: Alcohol Intake Using Three Consecutive Days Of Intermittent supporting

confidence: 91%

Subgroup-dependent effects of voluntary alcohol intake on behavioral profiles in outbred Wistar rats

Momeni

Roman

2014

Behavioural Brain Research

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“…Furthermore, OSU6162 blunted alcohol-induced dopamine output in the NAc of alcohol-naïve rats [196], indicating that OSU6162 has the ability to attenuate the rewarding effects of alcohol. In contrast, a more recent microdialysis study conducted in long-term drinking rats, showed that OSU6162, compared to vehicle-pretreatment, had no significant effect on the alcohol-induced dopamine peak [29].…”

Section: Preclinical Evidence For the Use Of Dopamine Stabilizers To mentioning

confidence: 91%

“…A series of experiments in outbred rats show that the dopamine stabilizer OSU6162 attenuates several alcohol-mediated behaviours including voluntary alcohol intake, alcohol withdrawal symptoms and cue/priming-induced reinstatement of alcohol seeking in long-term drinking rats [196]. Furthermore, OSU6162 blunted alcohol-induced dopamine output in the NAc of alcohol-naïve rats [196], indicating that OSU6162 has the ability to attenuate the rewarding effects of alcohol.…”

Section: Preclinical Evidence For the Use Of Dopamine Stabilizers To mentioning

confidence: 99%

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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“…Additionally, D 3 antagonists block cocaine and alcohol cue-induced reinstatement and have been under consideration for medications for psychostimulant addiction. The hypothesis that dysregulated dopamine tone contributes to the motivational effects of drug withdrawal and reinstatement remains viable, and dopamine modulators with appropriate neuropharmacological and pharmacokinetic profiles may be effective in treating certain aspects of addiction (for further reading, see Steensland et al, 2012).…”

Section: Partial Receptor Agonists -Dopamine Partial Agonistsmentioning

confidence: 99%