ANTAGONISM OF CERULETIDE, A CHOLECYSTOKININ ANALOG, TO THE NEUROCHEMICAL EFFECTS OF THE NONCOMPETITIVE N-METHYL-D-ASPARTATE (NMDA) RECEPTOR ANTAGONISTS, PHENCYCLIDINE AND MK-801, ON REGIONAL DOPAMINERGIC-NEURONS IN THE RAT-BRAIN

In the present study, we investigated the effects of ceruletide (CL), a cholecystokinin analog, on the neurochemical response to non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine (PCP) and MK-801, of the dopaminergic neuron systems in the discrete regions of the rat brain. Systemically administered PCP (7.5 mg/kg, i.p.) or MK-801 (1.0 mg/kg, i.p.) produced significant increases in the tissue contents of dopamine metabolite, homovanillic acid (HVA), in the prefrontal cortex, the nucleus accumbens and the olfactory tubercle but not in the nucleus caudatus putamen after 60 min. The effects of NMDA receptor antagonists in the nucleus accumbens and the prefrontal cortex were partially antagonized by pretreatment with CL (80 and 400-mu-g/kg, i.p., at 60 min prior to the drugs). While CL alone decreased the dopaminergic metabolism only in the nigrostriatal pathways in naive rats, the present results indicated that CL also attenuates the activities of the meso-limbic and meso-cortical dopaminergic neuron systems when these are enhanced by either PCP or MK-801.