Chronic ethanol consumption in rats produces residual increases in anxiety 4 months after withdrawal.

Department of Psychology, Manhattanville College, 2900 Purchase Street, Purchase, NY 10577, USA. <>
Behavioural Brain Research (Impact Factor: 3.39). 04/2008; 188(1):24-31. DOI: 10.1016/j.bbr.2007.10.009
Source: PubMed

ABSTRACT The present study investigated the long-term effects of ethanol consumption in rats. Subjects were maintained on either an ethanol (alcohol) (2.7-6.7%, v/v) or an isocaloric liquid control diet for 26 consecutive days (M=13.7 g/kg/day). Testing for working memory was conducted in a Morris water maze (2 trials/day for 8 days) and commenced after either a short (19 days) or long (120 days) abstinence period. This was followed by assessment of 72 h retention of passive avoidance. Animals were killed either 41 (short abstinence) or 152 days (long abstinence) post-ethanol and their brains stained with cresyl violet. Assessments of dorsal-ventral and medial-lateral cortical vertices were measured in sections derived from eight coronal planes extending +4.20 to -4.16 mm from Bregma. Results indicated that subjects in the ethanol/long abstinence group exhibited increased state anxiety due to their propensity to be thigmotaxtic (i.e., wall-hugging) in the water maze. Unfortunately, such a swim pattern precluded assessment of working memory in our subjects. No evidence of ethanol-induced memory decrements were observed on retention of passive avoidance. There was some evidence that animals in the ethanol/long abstinent group suffered cortical thinning and slight compression of the CA1 layer within the hippocampus, although age might have contributed to the former effect. It was concluded that chronic ethanol consumption increases anxiety even after an extended period of withdrawal and may conspire with age to affect cortical integrity.

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    ABSTRACT: Background Alcohol use disorders have been linked to increased anxiety, and enhanced central noradrenergic signaling may partly explain this relationship. Pharmacological interventions believed to reduce the excitatory effects of norepinephrine have proven effective in attenuating ethanol intake in alcoholics as well as in rodent models of ethanol dependence. However, most preclinical investigations into the effectiveness of these drugs in decreasing ethanol intake have been limited to acute observations, and none have concurrently assessed their anxiolytic effects. The purpose of these studies was to examine the long-term effectiveness of pharmacological interventions presumed to decrease norepinephrine signaling on concomitant ethanol self-administration and anxiety-like behavior in adult rats with relatively high levels of antecedent anxiety-like behavior.Methods Adult male Long-Evans rats self-administered ethanol on an intermittent access schedule for eight to ten weeks prior to being implanted with osmotic minipumps containing either an a1-adrenoreceptor antagonist (prazosin, 1.5 mg/kg/day), a β1/2-adrenoreceptor antagonist (propranolol, 2.5 mg/kg/day), a serotonin/norepinephrine reuptake inhibitor (duloxetine, 1.5 mg/kg/day) or vehicle (10% dimethyl sulfoxide). These drugs were continuously delivered across four weeks, during which animals continued to have intermittent access to ethanol. Anxiety-like behavior was assessed on the elevated plus maze before treatment and again near the end of the drug delivery period.ResultsOur results indicate that chronic treatment with a low dose of prazosin or duloxetine significantly decreases ethanol self-administration (P < 0.05). Furthermore, this decrease in drinking is accompanied by significant reductions in the expression of anxiety-like behavior (P < 0.05).Conclusions These findings suggest that chronic treatment with putative inhibitors of central noradrenergic signaling may attenuate ethanol intake via a reduction in anxiety-like behavior.
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