Abstract
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 µg/kg) moderately antagonized the sedative effect of apomorphine (0.1 mg/kg SC) and caerulein (25 µg/kg SC), whereas L-365,260 (1–10 µg/kg) significantly potentiated the actions of dopamine and CCK agonists. Concomitant administration of caerulein (15 µg/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 µg/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 byd-amphetamine (5 mg/kg IP). The CCK agonist caerulein (100 µg/kg SC) had a similar antiamphetamine effect. Devazepide (1–100 µg/kg) and L-365,260 (1 µg/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.
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Vasar, E., Harro, J., Lang, A. et al. Differential involvement of CCK-A and CCK-B receptors in the regulation of locomotor activity in the mouse. Psychopharmacology 105, 393–399 (1991). https://doi.org/10.1007/BF02244435
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DOI: https://doi.org/10.1007/BF02244435