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

Kõks, S., Abramov, U., Veraksits, A., Bourin, M., Matsui, T. and Vasar, E. (2003) CCK2 receptor-deficient mice have increased sensitivity of dopamine D2 receptors. Neuropeptides, 37 (1). pp. 25-29.

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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.

Item Type: Journal Article
Publisher: Elsevier
Copyright: © 2003 Elsevier Science Ltd.
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