Effect of a cholecystokinin tetrapeptide analogue on opioid reception under acute and chronic morphine administration

Effects of a modified CCK-4, a tetrapeptide fragment of cholecystokinin, on opioid reception and cAMP level were studied. The modified CCK-4 changed the ligand binding of the opioid receptors of μ-and δ-types in vitro. In vivo, it prevented changes in opioid reception caused by an acute morphine administration or by morphine withdrawal after its long-term administration. The CCK-4 analogue did not exert any effect in the state of intoxication after a long-term administration of morphine or even promoted the morphine effect. The injection of the CCK-4 analogue alone or together with morphine changed the forskolin-stimulated level of cAMP. These changes depended on the brain structure and the duration of the administration of morphine and the CCK-4 analogue.