Time-dependent quantifiable withdrawal from ethanol in the rat: Effect of method of dependence induction

Macey, Darrel J.; Schulteis, Gery; Heinrichs, Stephen C.; Koob, George F.

doi:10.1016/0741-8329(95)02030-6

Cited by 165 publications

(168 citation statements)

References 15 publications

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“…We measured the withdrawal signs (ventromedial distal limb flexion response, tail stiffness, and abnormal body posture and gait) (Macey et al, 1996;Roberto et al, 2004) at 2, 4, 6, and 8 hr after ethanol withdrawal in the ethanol-dependent group and compared them with similar measures from the naive group. Moderate behavioral signs of ethanol withdrawal were evident in all six rats tested at 2-8 hr after the termination of the ethanol treatment, a time frame corresponding to the electrophysiological recordings and microdialysis samples.…”

Section: Methodsmentioning

confidence: 99%

Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats

Roberto¹,

Madamba²,

Stouffer³

et al. 2004

J. Neurosci.

270

363

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The central nucleus of amygdala (CeA) is important in regulating alcohol consumption and plays a major role in the anxiogenic response to ethanol withdrawal. We showed previously that acute ethanol augments GABA A receptor-mediated IPSPs and IPSCs, possibly by a presynaptic mechanism. Here, we have examined the interaction of acute ethanol with the GABAergic system in chronic ethanol-treated (CET) rats using an in vitro CeA slice preparation and in vivo brain microdialysis. We found that in CeA slices from CET rats, the baseline evoked IPSP and IPSC amplitudes were increased, and paired-pulse facilitation ratios were lower than in naive rats, suggesting an increased GABAergic transmission after chronic ethanol treatment. Interestingly, acute ethanol (5-66 mM) significantly enhanced IPSPs and IPSCs equally in CET and naive rats, indicating a lack of tolerance for this effect of acute ethanol. Analysis of miniature IPSC frequency suggests that the increased GABAergic transmission by both acute and chronic ethanol arises from a presynaptic mechanism involving enhanced vesicular release of GABA. These data are supported by microdialysis studies showing that CET rats presented a fourfold increase in baseline GABA dialysate content compared with naive rats. In vivo administration of ethanol (0.1, 0.3, and 1.0 M) produced a dose-dependent increase in GABA release in the CeA dialysate in both CET and naive rats. These combined findings suggest that acute and chronic ethanol increases GABA release in CeA and support previous reports that the behavioral actions of ethanol are mediated, in part, by increased GABAergic transmission in the CeA.

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Section: Methodsmentioning

confidence: 99%

Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats

Roberto¹,

Madamba²,

Stouffer³

et al. 2004

J. Neurosci.

270

363

View full text Add to dashboard Cite

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“…Eight to 12 h after termination of ethanol vapor inhalation, withdrawal signs, including the ventromedial distal limb reflexion response, tail stiffness, and abnormal body posture were recorded using a rating scale as previously described (Macey et al, 1996). A subjective 0-to 2-point scale was used for each of these signs, with 0 representing undetectable, 1 representing moderate, and 2 representing severe withdrawal sign.…”

Section: Methodsmentioning

confidence: 99%

Reversal of Ethanol-Seeking Behavior by D1 and D2 Antagonists in an Animal Model of Relapse: Differences in Antagonist Potency in Previously Ethanol-Dependent versus Nondependent Rats

Liu

Weiss²

2002

The Journal of Pharmacology and Experimental Therapeutics

116

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Mesocorticolimbic dopamine (DA) transmission has been implicated in the consummatory and, more recently, the incentive-motivational aspect of ethanol's actions. The purpose of this study was to test whether ethanol-seeking behavior induced by an ethanol-associated contextual stimulus is sensitive to antagonism of DA transmission. Male Wistar rats were trained to orally self-administer 10% ethanol and to associate olfactory discriminative stimuli with the availability of ethanol (S ϩ ) versus nonreward (S Ϫ ). Ethanol-reinforced operant responding then was extinguished by withholding ethanol and the associated S ϩ . After reaching a predetermined extinction criterion, reinstatement tests were conducted in which the animals were presented noncontingently with only the S ϩ or S Ϫ . Exposure to the S ϩ but not the S Ϫ reinstated responding at the previously active lever. The D1 antagonist R(ϩ)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H -3-benzazepine hydrochloride (SCH23390; 5, 10, 50 g/kg s.c.) and the D2 antagonist eticlopride (5, 10, 50 g/kg s.c.) dose dependently decreased the number of S ϩ -induced responses and increased response latency. During a second test, conducted in the same rats, 3 weeks after withdrawal from a 12-day ethanol vapor inhalation procedure, the response-reinstating efficacy of the S ϩ remained unaltered. However, the potency of both DA antagonists to inhibit the S ϩ -induced drug-seeking response was significantly increased. The results confirm that ethanol-related contextual stimuli reliably elicit drug-seeking behavior and suggest that this effect requires activation of DA neurotransmission. The results also indicate that chronic ethanol exposure produces changes in D1 and D2 receptor function that lead to enhanced sensitivity to the behavioral effects of antagonists for these receptors.

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“…Although the molecular mechanisms remain to be elucidated, there is a broad consensus that acute ethanol inhibits NMDARs (Calton et al, 1998;Criswell et al, 2003;Hoffman et al, 1989;Kumari and Ticku, 2000;Loftis and Janowsky, 2003;Lovinger et al, 1989;Nie et al, 1994;Martin et al, 1995;Tabakoff and Hoffman, 1996;Tsai and Coyle, 1998;Woodward, 1999;Roberto et al, 2004b), whereas chronic ethanol treatment (CET) leads to a compensatory upregulation of these receptors resulting in increased NMDARmediated function after removal of ethanol (Gulya et al, 1991;Nagy et al, 2004). This increase in NMDARs, and especially the NR2B subunit, may contribute to the ethanol withdrawal syndrome (Kumari and Ticku, 2000;Nagy et al, 2004;Narita et al, 2000;Ripley and Little, 1995;Thomas et al, 1998) that is characterized by both behavioral and electrophysiological parameters (Macey et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Chronic Ethanol Exposure and Protracted Abstinence Alter NMDA Receptors in Central Amygdala

Roberto

Bajo

Crawford

et al. 2005

Neuropsychopharmacol

108

115

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We recently reported that chronic ethanol treatment (CET) and early withdrawal (2-8 h) altered glutamatergic transmission at both preand postsynaptic sites in central nucleus of the amygdala (CeA). Acute ethanol (44 mM) inhibited the NMDA receptor (NMDAR)-mediated EPSCs (NMDA-EPSCs) more in CeA neurons from CET rats than from naïve rats and also decreased paired-pulse facilitation (PPF) of NMDA-EPSCs only in CET rats. To determine whether these CET effects persisted after prolonged withdrawal, we recorded intracellularly in rat CeA slices and measured mRNA and protein expression of CeA NMDAR subunits from CET rats and those withdrawn from ethanol for 1 or 2 weeks. At 1 week withdrawal, acute ethanol decreased evoked NMDA-EPSC amplitudes and NMDA currents induced by exogenous NMDA (B20%) equally to that in naïve rats, indicating that CET effects on postsynaptic mechanisms reversed 1 week after CET cessation. However, acute ethanol still decreased PPF of NMDA-EPSCs, indicating that the acute ethanolinduced increase in glutamate release in CeA seen in CET rats was still present at this time. CET also significantly increased mRNA levels of NR1 and NR2B NMDAR subunits compared to control rats. At 1 week withdrawal, mRNA levels for NR1 and NR2B subunits were significantly decreased. These changes reversed at 2 weeks withdrawal. In Western blots, a significant increase in protein for all three subunits occurred in CeA from CET rats, but not after 1 and 2 weeks of withdrawal. These data indicate that CET induces reversible neuroadaptations in synaptic function, gene expression, and protein composition of NMDAR at CeA synapses. Neuropsychopharmacology (2006) 31, 988-996.

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Time-dependent quantifiable withdrawal from ethanol in the rat: Effect of method of dependence induction

Cited by 165 publications

References 15 publications

Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats

Increased GABA Release in the Central Amygdala of Ethanol-Dependent Rats

Reversal of Ethanol-Seeking Behavior by D1 and D2 Antagonists in an Animal Model of Relapse: Differences in Antagonist Potency in Previously Ethanol-Dependent versus Nondependent Rats

Chronic Ethanol Exposure and Protracted Abstinence Alter NMDA Receptors in Central Amygdala

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