It has been shown previously that chronic
ethanol treatment in mice leads to accelerated behavioural sensitization to psychomotor stimulants [Manley & Little (1997) J. Pharmacol. Exp. Ther., 281, 1330-1339], whilst repeated experience of
ethanol withdrawal sensitizes pathways underlying seizure activity (Becker & Hale (1993) Alcohol Clin. Exp. Res., 17, 94-98]. The aim of the current experiment was to investigate the consequences of repeated withdrawal from
ethanol on
amphetamine-induced behaviours in the rat and compare this with animals with electrical kindling of the amygdala, a procedure that has been shown to enhance
alcohol withdrawal seizures [Pinel et al. (1975) Can. J. Neurol. Sci., 2, 467-475]. For the kindling experiments,
electrodes were surgically implanted in the left basolateral amygdala and were stimulated daily at the afterdischarge threshold until a criterion of three consecutive stage 5
seizures was reached. Fully kindled rats showed a marginally significant reduction in sensitivity to the locomotor stimulant effects of acute
amphetamine compared with
sham and partially kindled rats which had experienced subthreshold stimulation of the amygdala.
Sham and partially kindled rats sensitized readily to the locomotor activating effects of
amphetamine (0.125 mg/kg) following repeated treatments, but the fully kindled rats did not. Fully kindled rats also failed to show place preference conditioning to
amphetamine (0.5 mg/kg). Rats, withdrawn three times from chronic
ethanol (liquid-diet), kindled more quickly to PTZ (30 mg/kg, i.p.) than rats with the same overall exposure to
ethanol (24 days) followed by a single withdrawal or control animals. However, there was no difference in the locomotor stimulating effects of acute
amphetamine (0.25-1 mg/kg, i.p.), the rate of sensitization to
amphetamine (0.125 mg/kg, i.p.) or
amphetamine induced conditioned place preference (1 mg/kg, i.p.). These observations suggest that, in rats, repeated withdrawal from a relatively mild chronic
ethanol treatment modulates neuronal systems that may also be involved in PTZ-induced kindling but not those involved in either the acute stimulant effects of
amphetamine or behavioural sensitization or appetitive conditioning following repeated
amphetamine administration. Behavioural changes following amygdala kindling differed from those following repeated
ethanol withdrawal, suggesting that withdrawal kindling from a mild
ethanol treatment differs in its effects from amygdala kindling.