Ethanol discrimination in the rat: lack of modulation by restraint stress and memantine

Koroś, Eliza; Kostowski, Wojciech; Danysz, Wojciech; Bieńkowski, Piotr

doi:10.1007/pl00005330

Cited by 8 publications

(5 citation statements)

References 41 publications

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“…Liu and Weiss (2003) found that conditioned stress increased alcoholseeking behavior in post-dependent rats, with conditioned stress and alcohol cues interacting to further facilitate alcohol seeking. However, despite these data, Koros et al (1999b) found that restraint stress did not affect the alcohol dose-response curve for alcohol discrimination.…”

Section: Stress During Withdrawal From Multiple Alcohol Exposures Incmentioning

confidence: 67%

“…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%

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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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Section: Stress During Withdrawal From Multiple Alcohol Exposures Incmentioning

confidence: 67%

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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“…In relation to alcohol, the discriminative stimulus effects of alcohol are not altered by acute restraint stress (Koros et al 1999) or acute foot shock stress (Bowen et al 1999). In contrast, social drinkers exposed to an acute social stressor prior to alcohol consumption report blunted subjective response to alcohol on ratings of “cheerful”, “focused”, and “outgoing” (de Wit et al 2003) and a subpopulation show blunted subjective stimulant effects of intravenously administered alcohol (Childs et al 2011).…”

Section: Discussionmentioning

confidence: 99%

The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats

et al. 2011

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Rationale and objective Repeated and/or heightened elevations in glucocorticoids (e.g., repeated stress) can promote escalated drug-taking behaviors and induce compromised HPA axis function. Given that interoceptive/subjective drug cues are a fundamental factor in drug-taking behavior, we sought to determine the effects of exposure to repeated elevations in the glucocorticoid corticosterone (CORT) on the interoceptive effects of alcohol in rats using drug discrimination techniques. Methods Male Long Evans rats trained to discriminate alcohol (1 g/kg, IG) vs. water were exposed to CORT (300 μg/ml) in the home cage drinking water for 7 days. The interoceptive effects of experimenter- and self-administered alcohol were assessed and HPA axis function was determined. Results The interoceptive effects of experimenter- and self-administered alcohol were blunted following CORT. Control experiments determined that this decreased sensitivity was unrelated to discrimination performance impairments or decreased CORT levels at the time of testing and was dependent on repeated CORT exposure. Susceptibility to compromised HPA axis function following CORT exposure was suggested by an altered pattern of CORT secretion and blunted CORT response following injection of the synthetic glucocorticoid dexamethasone. Conclusions These findings present a possible behavioral mechanism for escalated alcohol drinking during episodes of heightened elevations in glucocorticoids (e.g., stress). That is, during these episodes, individuals may consume more alcohol to achieve the desired interoceptive effects. Understanding these behavioral mechanisms may lead to a better understanding of factors that promote alcoholism and alcohol abuse in at risk populations.

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“…Koros and collegues [ 125 ] assessed the effects of restraint stress and memantine (2.25 or 4.5 mg/kg) on the dose-response curve of ethanol discrimination. Stress did not alter the rate of responding.…”

Section: Secondary Pharmacodynamicsmentioning

confidence: 99%

Pharmacodynamics of Memantine: An Update

Rammes¹,

Danysz²,

Parsons

2008

147

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Memantine received marketing authorization from the European Agency for the Evaluation of Medicinal Products (EMEA) for the treatment of moderately severe to severe Alzheimer´s disease (AD) in Europe on 17 th May 2002 and shortly thereafter was also approved by the FDA for use in the same indication in the USA. Memantine is a moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with strong voltage-dependency and fast kinetics. Due to this mechanism of action (MOA), there is a wealth of other possible therapeutic indications for memantine and numerous preclinical data in animal models support this assumption. This review is intended to provide an update on preclinical studies on the pharmacodynamics of memantine, with an additional focus on animal models of diseases aside from the approved indication. For most studies prior to 1999, the reader is referred to a previous review [196].In general, since 1999, considerable additional preclinical evidence has accumulated supporting the use of memantine in AD (both symptomatic and neuroprotective). In addition, there has been further confirmation of the MOA of memantine as an uncompetitive NMDA receptor antagonist and essentially no data contradicting our understanding of the benign side effect profile of memantine. THERAPEUTIC TARGETThe maximal therapeutically-relevant plasma concentration of memantine is around 1 M (see [55,203]). Brain extracellular fluid (ECF) concentration of around 0.8 M can be anticipated [102] and any receptor that expresses an affinity at, or below, the very low M range should be considered as a potential therapeutic target. Given this assumption, there are only four plausible known target types to date: the most likely is the NMDA receptor channel, but 5-hydroxy-tryptamine (5-HT 3 ) receptors [220] and 7 and/or 4 2 nicotinic receptors [11] should also be taken into consideration [11,37,165].The 7 and 4 2 nicotinic acetylcholine receptor and the 5-HT 3 receptor systems have been suggested to play a role in modulating CNS functions, including learning and memory. These receptors are structurally related, containing large extracellular ligand-binding domains and four transmembrane domains that are largely conserved. They exhibit considerable cross-pharmacology, e.g. high concentrations of the 7 nAChR agonist nicotine inhibit 5-HT 3 receptor-mediated responses, and high concentrations of the 5-HT 3 receptor agonist serotonin inhibit 7 nAChR-mediated responses. Based on this knowledge, it seems reasonable to investigate whether ligands specific for either receptor, might have affinity for both. NMDA RECEPTORS Fast Kinetics and Strong Voltage-DependencyMemantine blocks the NMDA receptor channel in an use-dependent manner, meaning that it can only gain access to the channel in the presence of agonist and remains largely *Address correspondence to this author at Preclinical R & D, Merz Pharmaceuticals, Eckenheimer Landstrasse 100, 60318 Frankfurt am Main, Germany; Tel: +49 69 1503368; E-mail: christopher.parsons@m...

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Ethanol discrimination in the rat: lack of modulation by restraint stress and memantine

Cited by 8 publications

References 41 publications

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

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

The effects of repeated corticosterone exposure on the interoceptive effects of alcohol in rats

Pharmacodynamics of Memantine: An Update

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