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Increased sensitivity to the stimulant effects of morphine conferred by anti-adhesive glycoprotein SPARC in amygdala

Abstract

Repeated administration of morphine substantially increases its locomotor-enhancing activity, a phenomenon termed locomotor sensitization. Here we show that secreted protein acidic and rich in cysteine (SPARC), an anti-adhesive glycoprotein present in the basolateral amygdala, contributes to the establishment of locomotor sensitization. The morphine-induced increase in SPARC levels in the basolateral amygdala persisted after morphine withdrawal and coincided with the duration of locomotor sensitization. Moreover, a single injection of morphine after SPARC infusion into the basolateral amygdala of previously uninjected mice substantially enhanced locomotor activity. Thus, SPARC may be an important element for establishing locomotor sensitization to morphine.

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Figure 1: Expression profile of SPARC protein in mouse brain after challenge.
Figure 2: Histology of morphine-induced alterations in BL SPARC mRNA levels.
Figure 3: Morphine-induced locomotor sensitization and upregulation of SPARC transcription.
Figure 4: Locomotor-enhancing response to acute morphine injection after microinfusion of SPARC.
Figure 5: The anti-adhesive effect of recombinant SPARC on neuronal cell lines.

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Acknowledgements

We thank N. Ishida for discussion and comments; M. Ohtomi, H. Miyazaki, M. Matsui, S. Oka, K. Nakagomi, S. Akiduki, Y. Kobayashi, T. Inoue and D. Yoshii for their assistance; and W. F. Goldman (MST Editing Company) for reviewing the manuscript. This work was supported by a grant from AIST, Ministry of International Trade and Industry, Japan.

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Correspondence to Mitsushi Ikemoto.

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Ikemoto, M., Takita, M., Imamura, T. et al. Increased sensitivity to the stimulant effects of morphine conferred by anti-adhesive glycoprotein SPARC in amygdala. Nat Med 6, 910–915 (2000). https://doi.org/10.1038/78675

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