The effects of chronic ethanol consumption and withdrawal on passive avoidance task and serum cholinesterase level in rats

Abstract

The effects of chronic ethanol consumption and ethanol withdrawal on serum cholinesterase (ChE) activity and passive avoidance task in rats were investigated. Ethanol was administered to rats by a modified liquid diet with 4.8% (v/v) ethanol for 3 days followed by 25 days on a liquid diet in which the ethanol concentration was increased to 7.2%. Control rats were pair fed with an isocaloric liquid diet not containing ethanol. ChE activity and blood ethanol concentration were measured at the end of the 4.8% ethanol consumption and after 25 days of ethanol (7.2%) feeding and, just before and 24th and 72nd h of ethanol withdrawal period. Passive avoidance acquisition was evaluated for 150 s (cut-off time) in three individual groups of ethanol-administered, ethanol withdrawn (24th and 72nd h of withdrawal) and control rats. Locomotor activity of the rats was also measured and evaluated. The daily ethanol consumption of the rats ranged from 11.5 to 14.9 g/kg. ChE activities of the ethanol feeding rats were significantly increased as compared to control rats at the 3rd (4.8% ethanol) and 25th days of chronic ethanol (7.2%) consumption and 24th h of ethanol withdrawal. It returned to control values at the 72nd h of the withdrawal. Blood ethanol levels were measured as 200 and 2.2 mg/dl at just before ethanol withdrawal and 24th h of ethanol withdrawal, respectively. Both chronic ethanol consumption and late period of ethanol withdrawal produced some significant decreases in passive avoidance latency of the rats. Our results suggest that chronic ethanol consumption and late period of ethanol withdrawal may be related to impairment of passive avoidance task in rats. In addition, serum ChE levels do not seem to be involved in impairment of cognitive functions in ethanol dependent-rats.

Introduction

A great deal is known about the actions of ethanol in the brain. Brain damage and/or impairments of learning and recent memory were seen often in patients suffering from chronic alcoholism (Schuckit, 2000). Alcohol dependents without clinically apparent cognitive impairment have been found to perform poorly on experimental memory tests adapted from comparative neuropsychology (Kessler et al., 1986, Bowden et al., 1992, Ambrose et al., 2001). Indeed, ethanol is generally known to impair learning and memory (Deitrich et al., 1989). Ethanol-induced memory impairment has been showed both in experimental and clinical studies (Matthews et al., 2002, Garcia-Moreno et al., 2002, Weissenborn and Duka, 2003, Land and Spear, 2004).

Cognitive impairment associated with ethanol has been focused on the central cholinergic system due to the results of cholinergic activity deficit in brain. It has been suggested that a positive correlation between some kind of dementia and neuronal cholinergic impairment (Smith and Swash, 1978, Schindler, 1989, Yamada and Nabeshima, 2000). Since degeneration of the basal forebrain cholinergic neurons occur early in the course of Alzheimer's disease and are correlated with cognitive deficits (Coyle et al., 1983, Winkler et al., 1998). Cholinesterase (ChE), an enzyme degrades acetylcholine (Ach), activity in the cerebrospinal fluid is assumed to be a biochemical marker for clinical diagnosis and prognosis of several central and peripheral nervous system dysfunction such as Alzheimer's disease and dementia as well as chronic alcoholism (Kluge et al., 1999). A recent study from our laboratory (Bilgi et al., 2003) has been shown that serum ChE activity was increased by chronic ethanol consumption and increased serum ChE activity was still observed after 24 h of ethanol withdrawal. In this study, ChE activity returned control levels at the 72nd h of ethanol withdrawal. The authors hypothesized that there might be a marked relationship between chronic ethanol consumption or ethanol dependence and ChE activity in rats (Bilgi et al., 2003). However, any real clinical or experimental evidence between ChE levels and some kind of dementia such as Alzheimer disease has not been shown yet.

In some preliminary experiments, we observed interestingly that ethanol withdrawal-induced amnesia in a passive avoidance task of Wistar rats. Thus, the aim of the present study was to investigate the effects of chronic ethanol administration and/or ethanol withdrawal on passive avoidance task in rats. This was done by measurement of passive avoidance in rats feeding ethanol-contained liquid diet during early and late periods of ethanol withdrawal. The authors also evaluated ChE levels in ethanol-dependent rats.