Cholecystokinin-A but not cholecystokinin-B receptor stimulation induces endogenous opioid-dependent antinociceptive effects in the hot plate test in mice.

The effects of intracerebroventricular administration of the cholecystokinin (CCK) analogue, BDNL, and the selective CCK-B agonist, BC 264, were determined using the hot plate test in mice. BDNL (0.2 nmol and 0.5 nmol) increased the jump and the paw lick latencies. These effects were blocked by the CCK-A antagonist MK-329 (0.02 mg/kg), supporting the involvement of CCK-A receptors in CCK-induced analgesia. In contrast, the selective CCK-B agonist BC 264 produced, at one dose (2.5 nmol), a slight decrease in the lick latency that was only antagonized by the CCK-B antagonist. Naloxone, but not naltrindole, antagonized BDNL-induced analgesia. The results suggest that activation of CCK-A receptors by BDNL leads to antinociceptive responses indirectly mediated by stimulation of mu-opioid receptors by endogenous enkephalins.