title: Evidence for a role of endogenous neurotensin in the development of sensitization to the locomotor stimulant effect of morphine.
abstract: This experiment was aimed at exploring the role of endogenous neurotensin in the development of sensitization to the locomotor stimulant effect of morphine. During the induction phase (Days 1, 3, 5 and 7), male Long-Evans adult rats were treated with the neurotensin antagonist SR-48692 (160, 320 or 640 microg/kg, i.p.) or its vehicle, followed by morphine (5.0 mg/kg, i.p.) or its vehicle, and their locomotor activity (ambulatory, non-ambulatory and vertical activity) was measured for 2 h. One week after the last injection, each group received a single injection of morphine (2.5 mg/kg, i.p.) and their locomotor activity was again measured for 2 h (sensitization test, day 14). Results show that SR-48692 alone did not change locomotion. Morphine stimulated locomotor activity, an effect that was stronger on day 7 than on day 1. The two higher doses of SR-48692 attenuated the acute stimulant effect of morphine and prevented the observed increase from day 1 to day 7. The sensitization test on day 14 showed that rats pre-treated with morphine alone displayed significantly stronger ambulatory and vertical activity than vehicle pre-treated rats, a sensitization effect that was attenuated by SR-48692. The present results suggest that endogenous neurotensin contributes to the acute locomotor stimulant effect of morphine and to the induction of its sensitization.
authors.affiliation: Centre de recherche Fernand-Seguin, Hôpital Louis-H. Lafontaine, Université de Montréal, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Lévesque
authors.forename: Caroline
authors.initials: C
authors.lastname: Lamarche
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Rompré
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects*; D009294:Narcotics / Q000494:pharmacology*; D009496:Neurotensin / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D013268:Stimulation, Chemical
chemical_list: D009294:Narcotics; D009496:Neurotensin; D009020:Morphine