Abstract
Neuropeptide cholecystokinin (CCK) has been shown to suppress ethanol intake, but it is not clear if CCK-2 receptors play any role in this effect. In the present study, locomotor and sedative effects of acute ethanol administration, but also voluntary ethanol intake and preference were studied in male and female mice with genetic invalidation of CCK-2 receptors (-/-). Ethanol 0.5g/kg induced significant reduction of locomotor activity in male mice lacking CCK-2 receptors not habituated to motility boxes, as compared to their wild-type littermates (+/+). This effect was significantly modified by previous habituation to testing conditions. No such effect was observed in female mice. However, in female wild-type mice habituated to motility boxes ethanol 1.0g/kg induced significant locomotor suppression compared to female mice lacking CCK-2 receptors. Duration of loss of righting reflex (ethanol dose 4.0 g/kg) was not altered in mice lacking CCK-2 receptors. However, blood ethanol concentration at regain of righting reflex was significantly lower in female mice lacking CCK-2 receptors compared to their wild-type littermates. Ethanol intake, but not preference, was increased in mice with invalidation of CCK-2 receptor gene independent of gender. Current results indicate altered behavioural effects of ethanol and modified ethanol intake in mice lacking CCK-2 receptors. Gender-dependent neurochemical alterations possibly underlying these effects are discussed.