Identification of a factor involved in morphine-induced reverse tolerance

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.165-165
• Main Authors: Ikemoto, Mitsushi, Takita, Masatoshi, Inoue, Koutarou
• Format: Article
• Language: eng ; jpn
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)48121-3

A repeated morphine administration frequently results in an alteration in behavioral response to morphine. In particular, locomotor activity is remarkably enhanced by chronic morphine exposure. This enhancement, termed locomotor sensitization, is sustained for a long term after cessation of morphine. However, the underlying molecular mechanism remains unknown. Here we show that the anti-adhesive glycoprotein SPARC (Secreted Protein Acidic and Rich in Cystein) in basolateral amygdala nucleus (BL) contributes to the persistence of locomotor sensitization to morphine. By subtraction cloning procedure, we identified SPARC gene as whose expression in BL was specifically augmented by repeated morphine administration. Chronic, but not acute, exposure to morphine conferred specific up-regulation of SPARC mRNA and SPARC protein in BL mediated through opioid receptor. Once established, the augmented level of SPARC mRNA persisted for 2 weeks after spontaneous withdrawal, consistent with the duration of locomotor sensitization. Furthermore, infusion of SPARC protein into BL of normal mice conferred locomotor sensitization to morphine by a single morphine administration alone. These results indicate that SPARC act as a principle component to establish long-lasting locomotor sensitization to morphine.