A behavioural pharmacological study on intracerebroventricularly administered CCK-8 related peptides in mice.

ABSTRACT

The sulfated form of cholecystokinin octapeptide (CCK-8) and ceruletide (CER), but not their non-sulfated forms of CCK-4, significantly decreased the rates of locomotor activity and rearing during the first 10 min test session 10 min after intracerebroventricular (ICV) administration at doses more than 25 and 3.125 mg, respectively. CER-S antagonized methylphenidate-induced hypermotility after ICV administration at a dose of 800 ng. Plasma levels of CER-like immunoreactivity (CER-LI) measured at 120 min after subcutaneous injection, when the locomotor suppressive activity induced by 100 and 200 micrograms was no longer observed, were similar to or much higher than that 30 min after ICV administration at a dose of 800ng, suggesting that the effects of ICV CER-S are not mediated by a peripheral redistribution. These findings indicate that (1) the structural requirement for the locomotor suppressive activity is sulfated tyrosine residue; (2) the behavioural effects of ICV-administered CCK-8-S and CER-S are due to their central actions and mediated by the/inhibition of the central dopamine (DA) function; and (3) CCK-8-S in the brain is functionally associated with the central DA system.