ACUTE TOLERANCE ASSOCIATED WITH A SINGLE OPIATE ADMINISTRATION - INVOLVEMENT OF N-METHYL-D-ASPARTATE-DEPENDENT PAIN FACILITATORY SYSTEMS

Mechanisms underlying the development of acute tolerance to the analge sic effect of opiates were investigated. In the rat tail-flick test, a dministration of naloxone (1 mg/kg, s.c.) 40 min after heroin (1 mg/kg , s.c.) was shown to induce hyperalgesia, indicative of a short-onset, opiate-activated pain facilitatory systems masking the opiate analges ia. Pretreatment with the N-methyl-D-aspartate receptor antagonist diz ocilpine maleate blocked, in a dose-dependent manner, the naloxone-ind uced hyperalgesia and potentiated the heroin-induced analgesia. Using a schedule of two successive injections of 1 mg/kg heroin, acute toler ance was indicated by a marked reduction (-52%) in analgesia induced b y the second dose. After pretreatment with dizocilpine maleate, the ac ute tolerance was abolished and the analgesic effects of both injectio ns of heroin were strongly potentiated. These observations indicate th at acute tolerance appears after the first exposure to opiates and ste ms from opiate activation of N-methyl-D-aspartate-dependent pain facil itatory systems. (C) 1998 IBRO. Published by Elsevier Science Ltd.