Cholecystokinin antagonizes morphine induced hypoactivity and hyperactivity in hamsters

Three experimental replications were used to test the effects of three doses (25, 50 or 75 micrograms/kg) of cholecystokinin octapeptide (CCK-8) on morphine induced changes in activity. For each dose of CCK-8, running wheel activity of golden Syrian hamsters was monitored for three hours following a series of two injections. The first injection consisted of either saline or CCK-8, the second of either saline or morphine sulfate (15 mg/kg). Thus, in each replication four groups were created: Group SAL/SAL (n = 8) received two saline injections, Group CCK/SAL (n = 8) an injection of CCK-8 followed by an injection of saline, Group SAL/MS (n = 8) an injection of saline followed by an injection of morphine and Group CCK/MS (n = 8) an injection of CCK-8 followed by an injection of morphine. Results indicated that a 25 micrograms/kg dose of CCK-8 blocked the hypoactivity elicited by morphine 40-60 min after opiate injection, whereas a 75 micrograms/kg dose of CCK-8 blocked the hyperactivity elicited by morphine 80-100 min after opiate injection. These findings are consistent with previous reports that CCK-8 antagonizes the effects of opiate agonists on a variety of behaviors and is supportive of the hypothesis that endogenous CCK-8 may antagonize endogenous opioid peptides in the control of behavior.