Effect of intracerebroventricular and systemic injections of caerulein, a CCK analogue, on electrical self-stimulation and its interaction with the CCKA receptor antagonist, L-364,718 (MK-329)

Systemic administration of caerulein (10-100 micrograms/kg SC), a potent analogue of cholecystokinin, caused a profound dose-related depression of variable-interval self-stimulation, followed by progressive recovery within 60 min. Intracerebroventricular injection of caerulein (3-1000 ng) was not more effective than systemic injection, while injections into the nucleus accumbens (3-100 ng bilaterally) were without detectable effect. Systemic injections of L-364,718 (70-700 micrograms/kg IP), a specific competitive antagonist of CCKA ("peripheral-type") receptors, had no effect on self-stimulation when given alone. When given in combination with caerulein, L-364,718 (200 micrograms/kg IP) significantly reduced the inhibitory effect of caerulein (30 micrograms/kg SC); however, this dose, and higher doses of L-364,718, failed to confer complete protection. It is concluded that self-stimulation performance may be subject to modulation by CCK receptors distributed predominantly in the peripheral nervous system and that some but not all of these receptors are CCKA receptors.