Differential involvement of CCK-A and CCK-B receptors in the regulation of locomotor activity in the mouse.
The influence of the CCK-A antagonist devazepide and the CCK-B/gastrin antagonist L-365,260 on the locomotor activity of mice was studied. Devazepide and L-365,260 had opposite effects on spontaneous locomotor activity, and on caerulein- and apomorphine-induced hypomotility in the mouse. Devazepide in high doses (0.1-1 mg/kg IP) reduced spontaneous motor activity, whereas L-365,260 at a high dose (1 mg/kg IP) increased the activity of mice. Devazepide (0.1-10 micrograms/kg) moderately antagonized the sedative effect of apomorphine (0.1 mg/kg SC) and caerulein (25 micrograms/kg SC), whereas L-365,260 (1-10 micrograms/kg) significantly potentiated the actions of dopamine and CCK agonists. Concomitant administration of caerulein (15 micrograms/kg SC) and apomorphine (0.1 mg/kg SC) caused an almost complete loss of locomotor activity in the mouse. Devazepide and L-365,260 (0.1-10 micrograms/kg) were completely ineffective against caerulein-induced potentiation of apomorphine hypomotility. Devazepide in high doses (0.1-1 mg/kg), reducing the spontaneous motor activity of mice, counteracted the motor excitation induced by d-amphetamine (5 mg/kg IP). The CCK agonist caerulein (100 micrograms/kg SC) had a similar antiamphetamine effect. Devazepide (1-100 micrograms/kg) and L-365,260 (1 micrograms/kg) reversed completely the antiamphetamine effect of caerulein. The results of present study reflect apparently distinct role of CCK-A and CCK-B receptors in the regulation of motor activity. The opposite effect of devazepide and L-365,260 on caerulein- and apomorphine-induced hypolocomotion is probably related to the antagonistic role of CCK-A and CCK-B receptor subtypes in the regulation of mesencephalic dopaminergic neurons. The antiamphetamine effect of caerulein is possibly linked to the stimulation of CCK-A receptors in the mouse brain, whereas the blockade of both subtypes of the CCK-8 receptor is involved in the antiamphetamine effect of devazepide.
Vasar
E
E
Psychopharmacology Laboratory, Tartu University, Estonia.
Harro
J
J
Lang
A
A
Pôld
A
A
Soosaar
A
A
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D020109:Devazepide; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002108:Ceruletide; D002766:Cholecystokinin; D000661:Amphetamine; D020109:Devazepide; D001058:Apomorphine