CCK₂ receptor-deficient mice have increased sensitivity of dopamine D₂ receptors

The present study supports a role of CCK₂ receptors in the regulation of dopamine neurones. In pharmacological studies conducted on male CCK₂ receptor-deficient mice the changes in the activity of dopamine system were established. A low dose of dopamine agonist apomorphine (0.1 mg/kg), stimulating the pre-synaptic dopamine receptors, induced significantly stronger suppression of locomotor activity in mutant mice (-/-) compared to their wild-type littermates (+/+). The administration of amphetamine (3-6 mg/kg), a drug increasing dopamine release, caused a dose-dependent stimulation of locomotor activity in wild-type mice. In mice lacking CCK₂ receptors, a lower dose of amphetamine (3 mg/kg) tended to suppress the motor activity, whereas the higher dose (6 mg/kg) induced the significantly stronger motor stimulation in mutant mice. Moreover, in the CCK₂ receptor-deficient mice the affinity of dopamine D₂ receptors, but not 5-HT₂ receptors, was increased. Altogether, the targeted genetic suppression of CCK₂ receptors increased the sensitivity of pre- and post-synaptic dopamine D₂ receptors.