Sedative action of cholecystokinin octapeptide on behavioral excitation by thyrotropin releasing hormone and methamphetamine in the rat.

Abstract

Intracerebroventricular (i.c.v.) injection of C-terminal octapeptide of cholecystokinin (CCK-8) in rats prolonged pentobarbital- and ethanol-induced sleeping time, but non-sulfated CCD-8 (CCK-8-NS) had no effect and caerulein showed a tendency to prolong the pentobarbital narcosis. On the other hand, i.c.v. injection of thyrotropin releasing hormone (TRH) shortened the sleeping time and the effect of CCK-8 was apparently antagonized by combined administration of TRH. Spontaneous locomotor activity in the late morning and early afternoon was not affected by CCK-8, but it increased following i.c.v. injection of CCK-8-NS. Hyperactivity produced by TRH and methamphetamine was suppressed by i.c.v. injection of CCK-8, while CCK-8-NS showed a tendency to enhance the methamphetamine-induced hyperactivity and caerulein had no effect. These results indicate that CCK-8 has a sedative action and antagonizes the behavioral excitation caused by TRH and methamphetamine, but that the effects of CCK-8-NS and caerulein were rather the opposite of those of CCK-8. In an additional experiment the TRH-induced body shaking response was not affected by combined administration of CCK-8.