Effects of acute and chronic cocaine administration on EEG and behaviour in intact and castrated male and intact and ovariectomized female rats.

ABSTRACT

Intact and gonadectomized male and female WAG/ Rij rats were used to study the effects of gender and gonadal hormones on the development of sensitization and tolerance to cocaine-induced changes in EEG and behaviour. The four groups of WAG/Rij rats differed in the number of spontaneously occurring spike-wave discharges ovariectomy decreased and castration increased the number of spike-wave discharges. This confirms that testosterone has antiabsence effects and that female gonadal hormones may promote the occurrence of spike-wave discharges. Cocaine [10 and 20 mg/kg, intraperitoneally (IP)] was administered before and after chronic cocaine administration (9 days, one daily injection with 10 mg/kg) and EEG and behaviour were monitored. Cocaine strongly suppressed the occurrence of spike-wave discharges before and after chronic administration in all four groups, although the decrease was less in the intact males. Sensitization or tolerance induced by cocaine on EEG could not be established. Acute cocaine administration eliminated explorative, automatic, and passive behaviour, whereas various stereotypical activities such as uncoordinated head and body movements and head swaying emerged. Differences between groups were observed as intact males were less likely than subjects in the three other groups to engage in intense stereotyped behaviour. These data suggest that testosterone inhibits EEG and behavioural effects of acute cocaine administration. All four groups displayed less head swaying and more uncoordinated head and body movements after chronic cocaine administration, suggesting that behavioural sensitization had occurred. Differences between the four groups had faded away. Although pharmacokinetic differences in levels of cocaine and benzoylecgonine between the four groups were found, they could not easily be related to the behavioural differences between groups.