1-AMINOCYCLOPROPANE CARBOXYLIC-ACID (ACPC) PREVENTS MU-OPIOID AND DELTA-OPIOID TOLERANCE

1-Aminocyclopropane carboxylic acid (ACPC), a partial agonist of the g lycine site on the NMDA receptor, prevents tolerance to the mu opioid morphine and the delta ligand [D-Pen(2),D-Pen(5)]enkephalin (DPDPE) wh en co-administered with the opioid. In contrast, ACPC does not signifi cantly influence tolerance to the kappa, opioid U50,488H or the kappa, ligand naloxone benzoylhydrazone (NalBzoH). The actions of ACPC are r estricted to tolerance. When given alone, ACPC has no analgesic action s in the tailflick assay and it does not change morphine's ED(50) in n aive mice. Chronic administration of ACPC alone for 5 days does not af fect the sensitivity of mice to morphine. ACPC also reverses preexisti ng tolerance. When mice are made tolerant to morphine over 5 days and then receive ACPC along with their morphine, analgesia returns to naiv e levels within 3 days despite the continued administration of morphin e. The actions of ACPC on opioid tolerance correspond closely with tho se previously described with both competitive and non-competitive NMDA antagonists.