Reinstatement of morphine-induced conditioned place preference in mice by priming injections.

B Ribeiro Do Couto,M A Aguilar,C Manzanedo,M Rodríguez-Arias,J Miñarro

doi:10.1155/np.2003.279

B Ribeiro Do Couto, M A Aguilar + Show 3 more

Open Access

https://doi.org/10.1155/np.2003.279

Copy DOI

Abstract

To construct a model of relapse of drug abuse in mice, the induction, we evaluated the extinction and reinstatement of morphine-induced place preference. In Experiment 1, we examined the effects of morphine (0, 2, 3, 5, 10, 20 and 40 mg/kg) in the conditioned place preference (CPP) paradigm. Mice showed CPP with 5, 10, 20 and 40 mg/kg. In Experiment 2, we evaluated the effects of two different extinction procedures. After conditioning with 40 mg/kg of morphine, the mice underwent daily extinction sessions of 60 or 15 min of duration. CPP was extinguished after seven and nine sessions, respectively. In Experiment 3, we tested the reinstating effects of several priming doses of morphine. Mice were conditioned with 40 mg/kg of morphine and underwent the daily 15 min extinction sessions until CPP was no longer evident. Then, the effects of morphine (0, 2, 3, 5, 10, 20, 40 mg/kg, i.p.) were evaluated. CPP was reinstated by doses from 5 mg/kg upward. The results show that morphine priming injections are effective in reactivating opiateseeking behavior in mice, and thus, the CPP paradigm might be useful to investigate the mechanisms underlying relapse of drug abuse.

Highlights

Relapse to drug use after prolonged periods of abstinence is a common feature of drug addiction and remains the primary problem in treating drug abuse
We have demonstrated that an extinguished morphine-induced conditioned place preference (CPP) can be reinstated by the non-contingent administration of different priming
Animals were conditioned with 40 mg/kg of morphine and after extinction were tested 30 min after the following doses of morphine (0, 2, 3, 5, 10, 20, 40 mg/kg). * p < 0.01, significant difference in time spent in preconditioning vs. post-conditioning sessions or reinstatement tests doses of morphine in mice

Summary

INTRODUCTION

Relapse to drug use after prolonged periods of abstinence is a common feature of drug addiction and remains the primary problem in treating drug abuse. After the postconditioning test on day 8 (Post C l), 3 animals were discarded due to weak CPP expression demonstrated by a low difference between the time spent in the drug-paired compartment in the post-C test and that spent in pre-C (

RESULTS

POST CONDITIONING

DISCUSSION