The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · Sep 1997
Prevention of tolerance to the antinociceptive effects of systemic morphine by a selective cholecystokinin-B receptor antagonist in a rat model of peripheral neuropathy.
The ability of pretreatment by the selective cholecystokinin-B (CCK(B)) receptor antagonist L-365,260 (0.2 mg/kg s.c.) to prevent the development of tolerance to the antinociceptive action of morphine was evaluated by a well-established rat model of unilateral peripheral mononeuropathy. The 4-day pretreatment regimens (saline, L-365,260 or morphine alone, or with the combination of L-365,260 and morphine) were begun on postoperative day 12. The experiments were performed on day 16, when the pain-related behavior reached a stable maximum. ⋯ The effect of acute morphine in this latter pretreatment group was dose dependent, naloxone reversible and similar to the effect of acute morphine seen in the saline-pretreated group. Our results suggest that in this well-characterized model of neuropathic pain, the development of tolerance to the antinociceptive effect of systemic morphine can be prevented by systemic coadministration of the CCK(B) antagonist L-365,260. We further show, that in contrast to a tonic activity of the endogenous opioidergic system, a tonic activity of the endogenous CCK system cannot be revealed in this rat model of neuropathic pain.