The increased ethanol preference in rats induced by choice, darkness, or drugs is reduced by ritanserin

Lin, Naili; Hubbard, J. I.

doi:10.1016/0361-9230(94)90226-7

Cited by 15 publications

(5 citation statements)

References 19 publications

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“…Ritanserin. Ritanserin was reported to decrease ethanol drinking by rats under continuous access conditions (Meert & Janssen, 1991;Panocka & Massi, 1992;Lin & Hubbard, 1994) and produced non-specific reductions in operant selfadministration (Wilson et al, 1998;Gallate & McGregor, 1999). Other studies report no effect of ritanserin administration on ethanol preference or intake (Myers & Lankford, 1993;Svensson et al, 1993).…”

Section: Clinically Ineffective Medicationsmentioning

confidence: 99%

Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism?

Egli

2005

Addiction Biology

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Evaluating medications in animal laboratory paradigms can reveal whether the compound is effective in an established alcoholism model, at clinically relevant doses and exposure conditions, when administered orally (or transdermally) and without serious limiting side effects. Positive outcomes constitute a possible discovery for relevance to alcoholism and, under favorable marketing conditions, encourage further development. Medication testing using animal models of alcoholism might also guide clinical testing by discriminating clinically effective from clinically ineffective compounds. This ability rests on whether there are tests or, more reasonably, batteries of tests having this discriminative ability. The present paper examines this possibility. Effects of naltrexone and acamprosate in animal paradigms which model behavioral aspects of alcoholism are reviewed and compared with the effects of compounds which have limited effects in alcoholics. It is not clear at present whether any single paradigm or combination of paradigms differentiates clinically effective from clinically limited compounds. Steps are suggested to improve the use of preclinical laboratory tests to predict which compounds are likely to be effective medications for reducing drinking and sustaining abstinence in human alcoholics.

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Section: Clinically Ineffective Medicationsmentioning

confidence: 99%

Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism?

Egli

2005

Addiction Biology

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“…Also the serotonergic (5‐HT) 2 antagonist ritanserin or the dopamine D 2 receptor agonist bromocriptine produced promising data in animals (Meert et al . ; Panocka & Massi ; Lin & Hubbard ; Ng & George ; Ng, O'Dowd & George ), but failed in clinical trials (Johnson et al . ; Johnson ).…”

Section: Introductionmentioning

confidence: 99%

Postdependent state in rats as a model for medication development in alcoholism

Meinhardt

Sommer

2014

Addiction Biology

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Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a 'Diagnostic and Statistical Manual of Mental Disorders IV/V-like' diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review.

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“…After the first reports (Meert et al 1990;Meert and Janssen 1991), the effect of ritanserin has been confirmed in several laboratories (Rammsayer and Vogel 1991;Panocka and Massi 1992;Lin and Hubbard 1994); moreover, attenuation of ethanol intake has been reported also following risperidone treatment at doses at which the drug is a selective 5-HT 2 antagonist (Panocka et al 1993c). Other studies, however, reported no reduction of alcohol intake following ritanserin administration.…”

Section: Introductionmentioning

confidence: 80%

“…Previous studies have shown that ritanserin does not reduce ethanol intake in genetically selected alcoholpreferring rats (Panocka et al 1993b), while it can attenuate ethanol intake in genetically heterogeneous rats with developed preference for 3 % ethanol (Meert et al 1990;Meert and Janssen 1991;Rammsayer and Vogel 1991;Panocka and Massi 1992;Lin and Hubbard 1994). The present paper was aimed at investigating the mechanism of action of ritanserin in the latter experimental model.…”

Section: Blood Alcohol Levelsmentioning

confidence: 90%

Possible mechanism of action for the attenuation of ethanol intake induced by ritanserin in rats

et al. 1996

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The 5-HT2 receptor antagonist, ritanserin, reduces alcohol intake in rats and the nucleus accumbens (NAC) has been proposed as a site of action for the drug. Recent microdialysis studies have shown that acute subcutaneous (SC) administration of ritanserin increases extracellular 5-HT levels in the NAC. The present study evaluated, in genetically heterogeneous rats with developed preference for 3% ethanol, whether the attenuation of ethanol intake induced by ritanserin might be related to its effect on the synaptic availability of 5-HT in the NAC. Damaging 5-HTergic neurons by intracerebroventricular infusion of 5,7-dihydroxytryptamine (5,7-DHT) abolished the effect of ritanserin on ethanol consumption. Injections of the 5-HT3 receptor antagonist MDL 72222 into the NAC significantly reduced the inhibitory effect of SC injection of ritanserin, 1 mg/kg, and completely abolished the effect of ritanserin, 0.1 mg/kg. Subcutaneous injections of MDL 72222, 0.3 mg/kg 3 times/day, suppressed the effect of SC ritanserin, 0.1 mg/kg. The present findings, together with those of previous experiments showing that the tryptophan hydroxylase inhibitor p-chlorophenylalanine abolishes the effect of ritanserin, support the hypothesis that its effect on ethanol intake may be due to increased synaptic availability of 5-HT into the NAC.

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The increased ethanol preference in rats induced by choice, darkness, or drugs is reduced by ritanserin

Cited by 15 publications

References 19 publications

Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism?

Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism?

Postdependent state in rats as a model for medication development in alcoholism

Possible mechanism of action for the attenuation of ethanol intake induced by ritanserin in rats

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