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      The CCKB antagonist PD-134,308 facilitates rewarding effects of endogenous enkephalins but does not induce place preference in rats.

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          Abstract

          The interaction between cholecystokinin and endogenous opioid systems on rewarding responses was examined. Motivational effects induced by peripheral administration of a complete inhibitor of enkephalin catabolism, RB 101 or the CCKB antagonist PD-134,308, and by both compounds in combination were evaluated in the conditioned place preference test in rats. RB 101 (5, 10, 20, 40 and 80 mg/kg, IP, and 20 mg/kg, IV) given alone produced a bell-shaped dose-effect function. A significant increase of the preference for the drug-associated compartment was only observed at doses of 10 and 20 mg/kg (IP). The effect observed with morphine was stronger, and all the doses used of this compound (1.25, 2.5 and 5 mg/kg, SC) were found to be active. These results suggest that the inhibitor of enkephalin catabolism has weak rewarding properties. Pretreatment with the CCKB antagonist PD-134,308 (0.1, 0.3, 1 and 3 mg/kg, IP) alone failed to produce a reliable aversion or preference on the paradigm studied. When PD-134,308 (0.3 mg/kg, IP) was coadministered with a subthreshold dose of morphine (0.6 mg/kg, SC) or RB 101 (5 mg/kg, IP), a conditioned place preference was observed, indicating that the CCKB antagonist facilitated the motivational responses induced by endogenous enkephalins as compared to morphine. This suggests that endogenous cholecystokinin, acting through CCKB receptors, modulates the rewarding effects of endogenous enkephalins.

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          Author and article information

          Journal
          Psychopharmacology (Berl.)
          Psychopharmacology
          Springer Science and Business Media LLC
          0033-3158
          0033-3158
          Jan 1996
          : 123
          : 2
          Affiliations
          [1 ] Departement de Pharmacologie Moleculaire et Structurale, Faculte de Pharmacie 4, Paris Cedex, France.
          Article
          10.1007/bf02246168
          8741934
          e4ecbd03-b26c-4c8e-8096-f61aa5471bc7
          History

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