Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains☆

Abstract

Epidemiological studies indicate significant co-morbid expression of alcoholism, anxiety, and depression. These symptoms are often under-diagnosed and under-treated and can worsen prognostic and treatment outcome for alcoholism. Nonetheless, a causal relationship between alcoholism and these conditions is yet to be established. In this study we sought to determine the effects of daily alcohol administration on the indices of anxiety and depression in two rat strains, one of which exhibits inherent depressive-like characteristics. Moreover, it was of relevance to examine the effects of a clinically useful antidepressant on alcohol-induced behavioral changes. Wistar-Kyoto (WKY) rats derived from Wistar stock show low levels of locomotor activity in an open field and high levels of immobility in the forced swim test (FST) which is considered a measure of their helplessness and hence are considered a putative animal model of depression. Adult female WKY and Wistar rats were exposed for 3 hrs daily to 95% ethanol vapor to achieve a mean blood alcohol level (BAL) of approximately 150 mg/dL. Controls were exposed to air in similar inhalation chambers. Sixteen to 18 hrs following 7 or 14 days of exposure to alcohol, locomotor activity (LCA) in open field, duration of time spent in the open arm of the elevated plus-maze (EPM), reflective of anxiety-like behavior and immobility in FST were evaluated. Alcohol exposure for 7 or 14 days reduced LCA only in Wistar rats but enhanced FST immobility in both strains at both time points. Only 14 day alcohol exposure reduced EPM open arm time in both WKY and Wistar rats. Daily treatment with desipramine (8 mg/kg) blocked all the changes induced by alcohol in both strains. Thus, subchronic (7 day) exposure to alcohol induces depressive-like characteristics in Wistar rats and exacerbates that of WKY rats. Chronic (14 day) exposure, however, also induces an anxiety-like effect in both strains. The depressive-and anxietylike behaviors induced by alcohol were blocked by daily treatment with a tricyclic antidepressant. It may be suggested that prophylactic treatment of alcoholics with an antidepressant prior to detoxification may improve treatment outcome for alcoholism.

Chronic alcohol exposure differentially affects activation of female locus coeruleus neurons and the subcellular distribution of corticotropin releasing factor receptors

“…In the present study, ethanol-treated animals spent less time engaged in all three measured exploratory behaviors in the EZM: time in the open arms, head dips, and standing, when compared to their control counterparts. These results are consistent with a previous study examining the effects chronic ethanol vapor exposure on Wistar and Wistar-Kyoto rats (Getachew et al 2008). In that study, animals were exposed to ethanol vapor daily for 7 or 14 days, and when behavioral measures were taken, ethanol exposed animals were shown to have increased depressive and anxiety-like behaviors on an elevated plus maze.…”

Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants

“…The inhalation chamber has the advantage of easily achieving and maintaining the targeted BAC (Kliethermes et al, 2004). Moreover, the variability in the alcohol concentration between similarly controlled chambers is minimal (Lee et al, 2000; Getachew et al, 2008, 2010). …”

Antidepressant effects of resveratrol in an animal model of depression

“…A time-sampling scoring technique was used whereby the predominant behavior – immobility or swimming – in each 5-s period of the 300-s test was recorded as previously described [38]. It is of relevance to indicate that WKY rats exhibit spontaneous immobility in the forced swim test; hence, there is no need to have a pretest exposure to forced swimming the day before as is customary in inducing helplessness in other strains [35, 37, 38, 43]. Moreover, it is our experience that the immobility of the rats in the FST is maintained albeit at slightly higher level, provided the test is carried out after one week of rest.…”

“…In this study we examined the antidepressant-like effect of resveratrol in a non-induced model of depression, the Wistar-Kyoto (WKY) rats. WKY rats are an inbred strain of rats that show depressive-like behavior, decreased BDNF expression, and decreased hippocampal volume in comparison to their control, Wistar rats [35-39]. These rats were initially developed as a normotensive control for the spontaneously hypertensive rats [40], but were later found to demonstrate exaggerated immobility in the forced swim test, a measure of helplessness or depressive-like behavior [41].…”