Resumption of ethanol seeking behaviour in rats

Chiamulera, Cristiano; Valerio, Enzo; Tessari, Michela

doi:10.1097/00008877-199501000-00006

Cited by 38 publications

(17 citation statements)

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“…Furthermore, we do not know whether the small oral priming dose of ethanol alone could have reinstated responding, or whether the environmental cues associated with ethanol availability and the orosensory properties of ethanol acted additively to induce reinstatement. In this context, it is worth noting that although contingent or injected ethanol have been previously reported to reinstate ethanol responding, this effect shows high variability and inconsistency (Chiamulera et al, 1995;Lê et al, 1998Lê et al, , 1999Vosler et al, 2001;Lê and Shaham, 2002).…”

Section: Discussionmentioning

confidence: 97%

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

Bäckström

Bachteler

Koch

et al. 2003

Neuropsychopharmacol

235

178

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The glutamatergic system plays an important role in mediating neurobehavioral effects of ethanol. Metabotropic glutamate receptors subtype 5 (mGluR5) are modulators of glutamatergic neurotransmission and are abundant in brain regions known to be involved in ethanol self-administration. Here, we studied the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a highly potent, noncompetitive mGlu5 receptor antagonist, on voluntary ethanol consumption and relapse behavior. For this purpose, we used two models for the measurement of relapse behavior: (i) reinstatement of ethanol-seeking behavior by drug-associated cues and (ii) the alcohol deprivation effect in long-term ethanol-consuming rats. In the first set of experiments, rats were trained to lever press for ethanol in the presence of a distinct set of cues. After extinction, the animals were exposed to the respective cues that initiated reinstatement of responding. A response-contingent ethanol prime further enhanced responding compared to the conditioned cues alone. Under these conditions, MPEP (0, 1, 3, and 10 mg/kg) attenuated ethanol seeking significantly and in a dose-related manner. However, at the highest dose, MPEP also decreased the number of inactive lever responses. In the second set of experiments, rats with 1 year of ethanol experience and repeated deprivation phases were used. A subchronic treatment with MPEP (twice daily; 0, 3, and 10 mg/kg) resulted in a significant and dose-dependent reduction of the alcohol deprivation effect (ADE). Although the same MPEP treatment regimen decreased baseline drinking, this effect was not as pronounced as on the ADE. These results show in two commonly used models of relapse to ethanol that pharmacological targeting of mGlu5 receptors may be a promising approach for the treatment of alcoholism.

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Section: Discussionmentioning

confidence: 97%

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

Bäckström

Bachteler

Koch

et al. 2003

Neuropsychopharmacol

235

178

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“…Effective behavioral methods that model "relapse" induced by alcohol-related stimuli may provide useful tools for the understanding of conditioning factors in relapse and their neurobiological basis. Reexposure to previously self-administered drugs has been shown to effectively reinstate drug self-administration in humans and laboratory animals (Stretch and Gerber 1973;Ludwig et al 1974;Davis and Smith 1976;Meyer and Mirin 1979;de Wit and Stewart 1983;Stewart and Wise 1992;Chiamulera et al 1995). However, craving or the desire to engage in drug-seeking behavior often occurs in the absence of the abused drug.…”

Section: Discussionmentioning

confidence: 99%

Reinstatement of Alcohol-Seeking Behavior by Drug-Associated Discriminative Stimuli after Prolonged Extinction in the Rat

Katner

1999

Neuropsychopharmacology

207

109

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(Wikler 1948). There is now ample evidence that conditioned stimuli associated with the availability or consumption of abused drugs enhance subjective feelings of craving and the motivation to engage in drug-taking behavior in humans (Childress et al. 1987a(Childress et al. , 1987b(Childress et al. , 1988O'Brien et al. 1990O'Brien et al. , 1992Ehrman et al. 1992;Kranzler and Bauer 1992;Robbins and Ehrman 1992). For example, abstinent alcohol users exposed to a bar-like environment worked (i.e., pressed a button which dispensed alcohol) harder to acquire alcohol and showed greater subjective and physiological responses than those exposed to a neutral setting (Ludwig et al. 1974). Similarly, abstinent opiate-dependent subjects reported increased craving in response to the presentation of drug-related stimuli compared to methadonemaintained patients (Childress et al. 1987a). Drug-related stimuli can modify drug-seeking behavior in animals as well. Behavioral tests involving acquisition, extinction, and reinstatement of operant respond-

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“…Testing motivation for alcohol involves a post-extinction return to pressing a bar previously associated with alcohol responding, but in the absence of alcohol available to drink (Backstrom et al 2004;Bienkowski et al 2000;Chiamulera et al 1995;Ciccocioppo et al 2002Ciccocioppo et al , 2003Ciccocioppo et al , 2004 ; Koros et al 1999b;Lê et al 1998Lê et al , 2003Liu and Weiss 2002a,b). Animals trained to lever press for access to alcohol in the presence of auditory or visual cues will not necessarily reinstate lever pressing to these cues after extended extinction (Katner et al 1999; see also Bienkowski et al 2000).…”

Section: Repeated Alcohol Withdrawals and The Alcohol-deprivation Effmentioning

confidence: 99%

“…Animals trained to lever press for access to alcohol in the presence of auditory or visual cues will not necessarily reinstate lever pressing to these cues after extended extinction (Katner et al 1999; see also Bienkowski et al 2000). However, non-contingent "priming" with alcohol reinstates responding on the "alcohol bar" (Chiamulera et al 1995; see review by . Likewise, when exposed to a combination of an olfactory cue for alcohol and a previously presented auditory or visual cue (Katner et al 1999;Bienkowski et al 2000), alcohol-seeking behavior is reinstated.…”

Section: Repeated Alcohol Withdrawals and The Alcohol-deprivation Effmentioning

confidence: 99%

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

2004

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Rationale-The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse.Objective and results-An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence-a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis.Conclusions-The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse-and with relapse an inability to limit an abusive pattern of alcohol intake. The "kindling"/stress hypothesis provides a clear strategy for future studies to explore the advancing neural adaptation proposed to contribute to the pathogenesis of alcoholism.

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Resumption of ethanol seeking behaviour in rats

Cited by 38 publications

References 0 publications

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

mGluR5 Antagonist MPEP Reduces Ethanol-Seeking and Relapse Behavior

Reinstatement of Alcohol-Seeking Behavior by Drug-Associated Discriminative Stimuli after Prolonged Extinction in the Rat

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

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