Neuroleptic-like properties of cholecystokinin analogs: Distinctive mechanisms underlying similar behavioral profiles depending on the route of administration

Ceruletide, an Analog of Cholecystokinin Octapeptide: New Perspectives on Its Efficacy

“…When peripherally administered to rodents, high doses (µg order) of ceruletide produced catalepsy, which is similar to that induced by antipsychotic drugs such as haloperidol, had inhibitory effects on spontaneous locomotor activity and dopamine agonist-induced hyperlocomotion, and also attenuated electrical self-stimulation and reinforced operant responding (14,19,24,43,52,62,97,103,104). These data suggest that peripherally administered ceruletide has an inhibitory effect on dopaminergic behaviors.…”

“…These data suggest that peripherally administered ceruletide has an inhibitory effect on dopaminergic behaviors. Some of these effects may be due to the stimulation of CCK A receptors, most likely in the periphery, because of the activity of CCK A receptor antagonists and a subdiaphragmatic vagotomy (14,19,24,97,98). However, devazepide, a CCK A receptor antagonist, and L-365,260, a CCK B receptor antagonist, modulated the effects of ceruletide on dopamine agonist-induced behaviors in mice in a different manner (52).…”

Analysis of expression of cholecystokinin in dopamine cells in the ventral mesencephalon of several species and in humans with schizophrenia.

“…5), one being that the action of neuroleptic drugs seems to be mediated via DAreceptor blockade (17). Moreover, it has been pointed out that CCK exerts neuroleptic-like effects (18)(19)(20)(21). It should therefore be of interest to analyze a possible role also for the coexisting peptide CCK in schizophrenia (22).…”