THE SELECTIVE CHOLECYSTOKTIN(B) RECEPTOR ANTAGONIST L-365,260 DIMINISHES THE EXPRESSION OF NALOXONE-INDUCED MORPHINE-WITHDRAWAL SYMPTOMS INNORMAL AND NEUROPATHIC RATS

The ability of a pretreatment with the cholecystokinin(B)-receptor (CC KB) antagonist L-365,260 to prevent the development of morphine depend ence was studied in normal and neuropathic (unilateral peripheral neur opathy) rats. A 4-day pretreatment regimen with two daily s.c. injecti ons of either saline+saline, saline+morphine (3.0 mg/kg) or L-365,260( 0.2 mg/kg)+morphine was used, and withdrawal was precipitated by an in jection of naloxone (1.0 or 2.0 mg/kg i.v.) at 24 h after the last pre treatment injection. After pretreatment with morphine alone, physical dependence developed in both normal and neuropathic rats. However, the incidence of teeth chattering and ptosis was higher in neuropathic ra ts. Pretreatment with the combination of L-365,260 and morphine preven ted the expression of teeth chattering, ptosis, diarrhea, writhing and piloerection, but was devoid of effects on the exploratory activity a mong both groups of rats. These results suggest that endogenous CCK ac ting on CCKB-receptors may be involved in the development of morphine dependence both in normal and neuropathic rats.