Discriminative Stimulus Effects of Ethanol

Kostowski, Wojciech; Bieńkowski, Piotr

doi:10.1016/s0741-8329(98)00035-4

Cited by 84 publications

(13 citation statements)

References 168 publications

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“…This limitation may be addressed by the utilization of a three-choice (e.g., alcohol, water, lysergic acid diethylamide-LSD) drug discrimination procedure (Grant, 1999), that could behaviorally capture a qualitative shift from the stimulus being less alcohol-like, and more like another stimulus (LSD, for example). Additionally, given the complexity of the alcohol discriminative stimulus (e.g., contribution of various transmitter systems: Helms, McCracken, Heichman, & Moschak, 2013; Hodge & Cox, 1998; Kostowski & Bieńkowski, 1999; Platt & Bano, 2011) it is unlikely that manipulation of one system (glutamate) would completely block expression of the interoceptive effects of alcohol, as we had predicted.…”

Section: Discussionmentioning

confidence: 75%

Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats

Jaramillo

Randall

Frisbee

et al. 2015

Alcohol

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Sensitivity to the interoceptive effects of alcohol is blunted following a period of exposure to the stress hormone corticosterone (CORT), an effect that is suggested to be related, in part, to glutamatergic neuroadaptations. Group II metabotropic glutamate receptors (subtypes 2 and 3; mGluR2/3) modulate several drug- and alcohol-related behaviors, including the interoceptive (discriminative stimulus) effects of alcohol. Therefore, we sought to determine if manipulation of mGluR2/3 would restore sensitivity to the interoceptive effects of alcohol following CORT exposure. Using a two-lever drug discrimination task, male Long-Evans rats were trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water. First, the effect of mGluR2/3 antagonism on the discriminative stimulus effects of alcohol was determined using LY341495 (0.3–3.0 mg/kg; intraperitoneal [IP]). Next, the effects of mGluR2/3 antagonism and activation were assessed in discrimination-trained animals exposed to CORT (300 μg/mL) in the home cage drinking water or water only, for 7 days. Following CORT exposure, decreased sensitivity to alcohol (1 g/kg) was observed. Pretreatment with the mGluR2/3 agonist LY379268 (1.0–3.0 mg/kg; IP), but not the mGluR2/3 antagonist (0.3–1.0 mg/kg; IP), restored sensitivity to alcohol. Additionally, in Water controls, mGluR2/3 antagonism and mGluR2/3 activation disrupted expression of the discriminative stimulus effects of alcohol. Together, these findings suggest that blunted sensitivity to the interoceptive effects of alcohol following an episode of heightened stress hormone levels may be due to adaptations in mGluR2/3-related systems. The ability of mGluR2/3 activation to restore sensitivity to alcohol under these conditions lends further support for the importance of these receptors under stress-related conditions.

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Section: Discussionmentioning

confidence: 75%

Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats

Jaramillo

Randall

Frisbee

et al. 2015

Alcohol

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“…Over the past 30 years, studies employing ethanol discrimination procedures in adult animals have contributed to our understanding of the neural mechanisms underlying the subjective effects induced by ethanol administration (see Kostowski and Bienkowski, 1999). For discrimination training, food-deprived animals are typically administered either ethanol or vehicle and placed in conditioning chambers outfitted with two levers.…”

Section: Introductionmentioning

confidence: 99%

Age Differences in Ethanol Discrimination: Acquisition and Ethanol Dose Generalization Curves Following Multiple Training Conditions in Adolescent and Adult Rats

Anderson

Spear

2013

Alcohol Clin Exp Res

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Background Adolescents and adults vary in sensitivity to many effects of ethanol, although it is unknown whether they also differ in their perception of ethanol’s subjective cues. The present study characterized ethanol discrimination in adolescent and adult male rats using a rapidly acquired Pavlovian conditioned approach procedure. Methods Ethanol at one of three training doses (0.75, 1.0 or 1.25 g/kg) served as either a positive (POS) or negative (NOS) occasion setter. Each 20-min training session consisted of eight 15-s presentations of two cue lights located on either side of a dipper delivering chocolate Boost®. For POS-trained rats, the cue lights reliably predicted 5-s presentations of chocolate Boost during ethanol but not saline sessions, with the opposite contingencies used for NOS-trained rats. Anticipatory approach behavior (head entries into the reward delivery area) in the presence and absence of the cue lights was used to calculate discrimination scores on ethanol and saline sessions. Following acquisition, various doses of ethanol (0–1.5 g/kg) were administered to establish generalization curves. Results Although animals of both ages responded differentially on ethanol and saline sessions by the end of acquisition, adults met criterion more quickly and had higher discrimination scores during reinforced sessions than adolescents. Whereas adolescents failed to demonstrate any dose-dependent responding during testing when trained with the 0.75 or 1.25 g/kg ethanol doses, adults demonstrated broader ethanol generalization during testing sessions following training with all three ethanol doses. Among adolescents trained with 1.0 g/kg ethanol, less generalization occurred relative to adults. Conclusions Adolescents were less sensitive to ethanol’s interoceptive effects, indicating that ethanol is likely a more salient cue for adults than adolescents. These findings contribute to evidence that suggests adolescent-typical insensitivity to internal cues that typically limit ethanol consumption may contribute to the elevated intake commonly reported during this developmental period.

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“…Bienkowski and Kostowski [33] also reported a similar finding in that the sulfated derivative of DHEA, DHEAS, was ineffective at blocking the discriminative-stimulus effects of ethanol. Thus, the effects of DHEA on the discriminative-stimulus effects of ethanol are similar to those of RO15-4513, a partial inverse agonist at the benzodiazepine receptor site, which negatively modulates the GABA A receptor complex and has only been shown to modestly attenuate the subjective effects of ethanol (for review, see [14]). When these data are considered together, there seems to be little evidence to suggest that compounds that negatively modulate the GABA A receptor alter the discriminative-stimulus effects of ethanol even though these drugs can attenuate some of the other behavioral effects of ethanol.…”

Section: Importance Of the Gabaa System In The Behavioral Effects mentioning

confidence: 98%

“…Although a variety of neurotransmitters and signaling pathways have been shown to be involved in the behavioral effects of ethanol (e.g., [14–16]), central GABAergic activity is widely accepted to be one of the most important components of ethanol's effects as a CNS depressant [17, 18]. Behaviorally, this supposition is supported by research showing that benzodiazepines and barbiturates that positively modulate the GABA A receptor complex can substitute for ethanol in drug-discrimination procedures [19, 20].…”

Section: Importance Of the Gabaa System In The Behavioral Effects mentioning

confidence: 99%

Neurosteroid Binding Sites on the GABA_AReceptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence

Hulin

Amato

Porter

et al. 2011

Advances in Pharmacological Sciences

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Despite the prevalence of alcohol abuse and dependence in the US and Europe, there are only five approved pharmacotherapies for alcohol dependence. Moreover, these pharmacotherapeutic options have limited clinical utility. The purpose of this paper is to present pertinent literature suggesting that both alcohol and the neurosteroids interact at the GABAA receptor complex and that the neurosteroid sites on this receptor complex could serve as new targets for the development of novel therapeutics for alcohol abuse. This paper will also present data collected by our laboratory showing that one neurosteroid in particular, dehydroepiandrosterone (DHEA), decreases ethanol intake in rats under a variety of conditions. In the process, we will also mention relevant studies from the literature suggesting that both particular subtypes and subunits of the GABAA receptor play an important role in mediating the interaction of neurosteroids and ethanol.

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Discriminative Stimulus Effects of Ethanol

Cited by 84 publications

References 168 publications

Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats

Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats

Age Differences in Ethanol Discrimination: Acquisition and Ethanol Dose Generalization Curves Following Multiple Training Conditions in Adolescent and Adult Rats

Neurosteroid Binding Sites on the GABA_AReceptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence

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Discriminative Stimulus Effects of Ethanol

Cited by 84 publications

References 168 publications

Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats

Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats

Age Differences in Ethanol Discrimination: Acquisition and Ethanol Dose Generalization Curves Following Multiple Training Conditions in Adolescent and Adult Rats

Neurosteroid Binding Sites on the GABAAReceptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence

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Product

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Neurosteroid Binding Sites on the GABA_AReceptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence