CONDITIONED PLACE PREFERENCE - NO TOLERANCE TO THE REWARDING PROPERTIES OF MORPHINE

The effect of repeated morphine administration on conditioned place pr eference (CPP) using a novel treatment schedule, i.e., drug treatment was always contingent with the conditioned environmental stimuli, was investigated. We also examined whether changes in the mu- and kappa-op ioid receptor binding occurred in the brain of morphine-treated animal s. Intraperitoneal (i.p.) administration of morphine (2 and 10 mg/kg) induced a place preference after 8 daily conditioning trials (4 morphi ne injections on alternate trials), the level of preference being the same with the two doses of the opiate. No change in place preference w as observed in the morphine-treated rats at 2 mg/kg, when animals were further trained up to a total of 32 conditioning trials (16 morphine injections). Conversely, after 20 conditioning trials (10 morphine inj ections), a stronger CPP response developed in the morphine-treated ra ts at 10 mg/kg. Signs of morphine withdrawal were never detected in mo rphine-treated rats during the experiment. Loss of body weight (index of opiate dependence) was not observed either 24 h or 48 h after the l ast morphine administration. mu- and kappa-opioid receptor density and affinity were not affected by repeated morphine administrations at ei ther dose. The results demonstrate that no tolerance develops to the r ewarding properties of morphine. Indeed, a sensitisation effect may oc cur at increasing doses of the opiate. Furthermore, changes in the rew arding effect of morphine are not dependent upon alterations in opioid receptors involved in the reinforcing mechanisms.