Aversive conditioning following repeated withdrawal from ethanol and epileptic kindling

Abstract

Repeated withdrawal from ethanol, a procedure which resembles amygdala kindling in increasing seizure sensitivity, impairs the acquisition of fear conditioning (Stephens et al., 2001, Eur. J. Neurosci.,14, 2023-31). In contrast, rats previously kindled by repeated electrical stimulation of basolateral amygdala, or repeated administration of pentylenetetrazol, showed increased suppression of operant responding during the presentation of a stimulus conditioned to footshock when conditioning took place several weeks following the kindling experience. Neither form of kindling nor repeated ethanol withdrawal altered taste aversion conditioning, though rats treated chronically with ethanol and given a single withdrawal experience showed enhanced taste aversion conditioning. These results suggest that, despite evidence suggesting a common neuronal mechanism underlying seizure sensitivity following these types of kindling, they differ in their effects on fear conditioning.

Effects of acute withdrawal on ethanol-induced conditioned place preference in DBA/2J mice

“…This explanation predicts that other forms of learning not involving ethanol reward would also be enhanced if training occurred during acute withdrawal, a possibility that could be tested in future studies. However, facilitation of learning seems an unlikely explanation in light of previous studies showing that withdrawal after chronic ethanol exposure interferes with associative learning (e.g., Ripley et al 2003, 2004). Another possibility is that the enhancement in CPP is somehow related to the suppressant effect of acute withdrawal on ethanol stimulated activity.…”

Ethanol modulation of synaptic plasticity

“…This suggests that chronic ethanol exposure chemically conditions the BLA such that the mechanisms responsible for the initiation and expression of long-term synaptic plasticity are usurped and up-regulated by the treatment itself. This BLA “Ethanol-LTP” would help explain both the altered fear/aversive-memory formation (Bertotto et al, 2006; Quadros et al, 2003; Ripley et al, 2003) and the increased anxiety following chronic alcohol exposure.…”

Previous experience of ethanol withdrawal increases withdrawal-induced c-fos expression in limbic areas, but not withdrawal-induced anxiety and prevents withdrawal-induced elevations in plasma corticosterone

“…Although most studies have concentrated on the effects of repeated ethanol withdrawal on seizure activity during withdrawal (Brown et al 1988;Lechtenberg and Worner 1991), a phenomenon readily modelled in rodents (Becker and Hale 1993;Ghozland et al 2005;Mhatre and Gonzalez 1999;Stephens et al 2001;Veatch and Becker 2002), attention has been given more recently to the effects of repeated withdrawal on other behavioural and physiological symptoms of withdrawal (Holter et al 1998;Overstreet et al 2002) and to long-term consequences of repeated withdrawal experience on emotional and cognitive function (Duka et al 2004;Ripley et al 2003a;Stephens et al 2001;Townshend and Duka 2003). A link has also been drawn between repeated withdrawal and binge drinking (Duka et al 2004;Stephens et al 2005;Townshend and Duka 2005).…”