CCK2 receptor-deficient mice have increased sensitivity of dopamine D2 receptors.
The present study supports a role of CCK(2) receptors in the regulation of dopamine neurones. In pharmacological studies conducted on male CCK(2) 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 CCK(2) 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 CCK(2) receptor-deficient mice the affinity of dopamine D(2) receptors, but not 5-HT(2) receptors, was increased. Altogether, the targeted genetic suppression of CCK(2) receptors increased the sensitivity of pre- and post-synaptic dopamine D(2) receptors.
Kõks
S
S
Department of Physiology, Biomedicum, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. sulev.koks@ut.ee
Abramov
U
U
Veraksits
A
A
Bourin
M
M
Matsui
T
T
Vasar
E
E
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004594:Electrophysiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D011869:Radioligand Assay; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000172:deficiency* / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D018491:Dopamine Agonists; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D017448:Receptors, Dopamine D2; D013134:Spiperone; D001058:Apomorphine