Chronic ethanol consumption in rats produces residual increases in anxiety 4 months after withdrawal.
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: Some evidence suggests that adolescents are more sensitive than adults to ethanol-induced cognitive deficits and that these effects may be long-lasting. The purpose of Exp 1 was to determine if early-mid adolescent [postnatal day (P) 28-48] intermittent ethanol exposure would affect later learning and memory in a Pavlovian fear conditioning paradigm differently than comparable exposures in adulthood (P70-90). In Exp 2 animals were exposed to ethanol during mid-late adolescence (P35-55) to assess whether age of initiation within the adolescent period would influence learning and memory differentially. Male Sprague-Dawley rats were given 4g/kg i.g. ethanol (25%) or water every 48h for a total of 11 exposures. After a 22 day non-ethanol period, animals were fear conditioned to a context (relatively hippocampal-dependent task) or tone (amygdala-dependent task), followed by retention tests and extinction (mPFC-dependent) of this conditioning. Despite similar acquisition, a deficit in context fear retention was evident in animals exposed to ethanol in early adolescence, an effect not observed after a comparable ethanol exposure in mid-late adolescence or adulthood. In contrast, animals that were exposed to ethanol in mid-late adolescence or adulthood showed enhanced resistance to context extinction. Together these findings suggest that repeated ethanol imparts long-lasting consequences on learning and memory, with outcomes that differ depending on age of exposure. These results may reflect differential influence of ethanol on the brain as it changes throughout ontogeny and may have implications for alcohol use not only throughout the developmental period of adolescence, but also in adulthood.Behavioural brain research 08/2013; 256. DOI:10.1016/j.bbr.2013.08.013 · 3.39 Impact Factor
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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.07/2014; 4(4). DOI:10.1002/brb3.230
European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL; 09/2011