Supraspinal neurotensin-induced antianalgesia in mice is mediated by spinal cholecystokinin

Intracerebral injection of neurotensin into specific brain loci in rats pro duces hyperalgesia due to the release of cholecystokinin (CCK) in the spina l cord. The present purpose was to show in another species that neurotensin can antagonize the antinociceptive action of morphine through the spinal C CK mechanism in mice. Neurotensin given intracerebroventricularly (i.c.v.) at doses higher than 100 ng produced antinociception in the tail flick test . However, at lower doses between 1 pg to 25 ng, neurotensin antagonized th e antinociceptive action of morphine given intrathecally (i.t.), thus demon strating the antianalgesic activity of neurotensin. The rightward shift in the morphine dose-response curve produced by i.c.v. neurotensin was elimina ted by an i.t. pretreatment with CCK8 antibody (5 mu l of antiserum solutio n diluted 1:1000). I.t. administration of lorglumide, a CCKA-receptor antag onist (10-1000 ng), and PD135,158, a CCKB-receptor antagonist (250 - 500 ng ), also eliminated the antianalgesic action of neurotensin. Thus, the mecha nism of the antianalgesic action of neurotensin given i.c.v. involved spina l CCK. This mode of action is similar to that for the antianalgesic action of supraspinal pentobarbital which also involves spinal CCK.