Flumazenil blockade of anxiety following ethanol withdrawal in rats

Moy, Sheryl S.; Knapp, Darin J.; Criswell, Hugh E.; Breese, George R.

doi:10.1007/s002130050303

Cited by 87 publications

(90 citation statements)

References 33 publications

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“…For example, withdrawal from alcohol liquid diet, chronic injections, vapor exposure, or consumption from a single drinking bottle increase anxiety-like behavior in mice that persists for up to 48 h after alcohol exposure (Costall et al, 1988;Joshi et al, 2005;Kliethermes et al, 2004;Prediger et al, 2006;Sparta et al, 2007). Similar results have been obtained in rat models showing increased anxiety-like behavior during acute and early withdrawal from an alcohol liquid diet (Baldwin et al, 1991;Moy et al, 1997;Pandey et al, 1999;Rassnick et al, 1993). In the present study, we observed increased anxiety-like behavior in non-dependent mice 1 day after voluntary alcohol drinking as measured by an open-field thigmotaxy assay.…”

Section: Discussionsupporting

confidence: 55%

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

Stevenson

Schroeder

Nixon

et al. 2008

Neuropsychopharmacol

133

102

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Alcoholism and depression show high degrees of comorbidity. Clinical evidence also indicates that depression that emerges during abstinence from chronic alcohol use has a greater negative impact on relapse than pre-existing depression. Although no single neurobiological mechanism can account for the behavioral pathologies associated with these devastating disorders, converging evidence suggests that aspects of both alcoholism and depression are linked to reductions in hippocampal neurogenesis. Here, we report results from a novel preclinical behavioral model showing that abstinence from voluntary alcohol drinking leads to the emergence of depressionlike behavior and reductions in neurogenesis. C57BL/6J mice were allowed to self-administer ethanol (10% v/v) vs H 2 O in the home cage for 28 days. Alcohol was then removed for 1 or 14 days, and mice were tested in the forced swim test to measure depression-like behavior. After 14 days, but not 1 day of abstinence from alcohol drinking, mice showed a significant increase in depression-like behavior. The significant increase in depression-like behavior during abstinence was associated with a reduction in proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) immunoreactivity in the dentate gyrus of the hippocampus indicating that both the number of proliferating neural progenitor cells (NPC) and immature neurons were reduced, respectively. The number of NPCs that were labeled with bromo-deoxyuridine (BrdU) at the beginning of alcohol exposure was not altered indicating that survival of NPCs is not linked to abstinence-induced depression. Chronic treatment (14 days) with the antidepressant desipramine during abstinence prevented both the emergence of depression-like behavior and the reduction in hippocampal neurogenesis indicating that abstinence-induced depression is associated with structural plasticity in the hippocampus. Overall, the results of this study support the conclusion that profound functional (ie behavioral) and structural changes occur during abstinence from alcohol use and suggest that antidepressant treatment may alleviate some of these pathological neurobehavioral adaptations.

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Section: Discussionsupporting

confidence: 55%

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

Stevenson

Schroeder

Nixon

et al. 2008

Neuropsychopharmacol

133

102

View full text Add to dashboard Cite

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“…In general, behavioral assessments were conducted after 15 days of exposure to the ED, between 5 and 6 h after the removal of the ethanol. This time point was selected on the basis of previous observations of anxiety-like behavior in our laboratory (e.g., Knapp et al, 1998;Moy et al, 1997Moy et al, , 2000.…”

Section: Liquid Dietmentioning

confidence: 99%

Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors

Overstreet

Knapp

Breese

2004

Pharmacology Biochemistry and Behavior

159

153

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Previous work demonstrated that rats subjected to multiple withdrawals from chronic ethanol exhibit a sensitization of anxiety-like behavior compared to animals withdrawn from treatment with an equal but continuous amount of ethanol. This study sought to examine whether corticotropin-releasing factor (CRF) could modulate this ethanol-withdrawal-induced anxiety-like behavior. Initially, rats were administered with CRF (1 μg) or vehicle intraventricularly on two occasions 5 days apart while on control diet (CD) followed by exposure to 7% ethanol diet (ED) for 5 days, with social interaction assessed 5 h into withdrawal. Social interaction was significantly reduced in the CRF-treated animals compared to vehicle-treated rats and vehicle-and CRF-treated rats maintained on CD, indicative that CRF given before ethanol exposure was capable of inducing an adaptive change that sensitized withdrawal-induced anxiety-like behavior. Next, the CRF 1 receptor antagonist CRA1000 (3 mg/kg, systemically), the CRF 2 receptor antagonist antisauvagine-30 (20 μg intraventricularly), or vehicle was injected 4 h after the ethanol was removed following the first and second cycles of chronic ethanol exposure and the effect on the multiple-withdrawal-induced anxiety-like behavior determined after the third withdrawal cycle. The CRF 1 receptor antagonist blocked the reduced social interaction behavior, whereas the CRF 2 receptor antagonist was without effect. Similar pretreatment with another CRF 1 receptor antagonist CP-154,526 (10 mg/kg systemically) during the first and second withdrawals also counteracted anxiety-like behavior. These findings indicate that the CRF system and CRF 1 receptors play key roles in the adaptive change responsible for the anxiety-like behavior induced by repeated withdrawals from chronic ethanol.

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“…After adaptation to the laboratory for 5 days, they were individually housed and placed on a nutritionally complete lactalbumin-dextrose diet for 3 days (Frye et al 1983;Moy et al 1997). The experimental rats were exposed to a diet containing ethanol (ED; 7%, w/v), while control rats remained on the control diet in which the dextrose replaced the ethanol isocalorically.…”

Section: Animalsmentioning

confidence: 99%

A 5-HT1A agonist and a 5-HT2c antagonist reduce social interaction deficit induced by multiple ethanol withdrawals in rats

et al. 2003

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Rationale-Repeated withdrawals from chronic forced ethanol exposure sensitize animals to withdrawal-induced deficits in social interaction behavior. The deficits in social interaction behavior following withdrawal from continuous ethanol exposure can be reduced following acute treatments with 5-HT 2C antagonists or 5-HT 1A agonists.Objectives-The present study investigated whether prior treatment with these serotonergic agents during early withdrawals in rats subjected to repeated withdrawals from ethanol exposure would ameliorate the social interaction deficits observed following the final withdrawal.Methods-Sprague-Dawley rats were exposed to three cycles of 5 days forced ethanol (7%, w/v), with 2 days of control diet after the first and second cycles. Drugs were administered IP 4 h after removal of ethanol on the first and second cycles but not the third in one group and 4.5 h after removal of ethanol on the third cycle in another. The social interaction test was performed 5 h after removal of ethanol on the third cycle. Drugs tested included SB-242084, a 5-HT 2C antagonist; buspirone, a 5-HT 1A partial agonist; WAY-100635, a 5-HT 1A antagonist; ketanserin, a 5-HT 2A antagonist; ritanserin, a mixed 5-HT 2A/2C antagonist; and Ro-601075, a 5-HT 2C agonist.Results-Both SB-242084 and buspirone reduced ethanol withdrawal-induced deficits in social interaction when given either acutely 30 min before the test or at 4 h after withdrawal from the first and second cycles. WAY-100635 and ketanserin were completely ineffective regardless of mode of treatment. In contrast, the 5-HT 2C agonist, Ro-601075, accentuated the withdrawal-induced deficit in social interaction behavior in rats exposed to either 4.5 or 7% ethanol diet. Conclusions-These results support the utility of 5-HT 1A agonists and 5-HT 2C antagonists in reducing anxiety-like behavior induced by ethanol withdrawal and reducing the adaptive changes associated with repeated withdrawals.

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Flumazenil blockade of anxiety following ethanol withdrawal in rats

Cited by 87 publications

References 33 publications

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors

A 5-HT1A agonist and a 5-HT2c antagonist reduce social interaction deficit induced by multiple ethanol withdrawals in rats

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