Work

Genetic Dissociation of Opiate Tolerance and Physical Dependence in δ-Opioid Receptor-1 and Preproenkephalin Knock-Out Mice

Year: 2002

Type: article

Abstract: Previous experiments have shown that mice lacking a functional δ-opioid receptor (DOR-1) gene do not develop analgesic tolerance to morphine. Here we report that mice lacking a functional gene for the endogenous ligand preproenkephalin (ppENK) show a similar tolerance deficit. In addition, we found that the DOR-1 andppENK knock-outs as well as the NMDA receptor-deficient 129S6 inbred mouse strain, which also lacks tolerance, exhibit antagonist-induced opioid withdrawal. These data demonstrate that although signaling pathways involving ppENK, DOR, and NMDA receptor are necessary for the expression of morphine tolerance, other pathways independent of these factors can mediate physical dependence. Moreover, these studies illustrate that morphine tolerance can be genetically dissociated from physical dependence, and thus provide a genetic framework to assess more precisely the contribution of various cellular and molecular changes that accompany morphine administration to these processes.

Source: Journal of Neuroscience

DOI: 10.1523/jneurosci.22-24-10906.2002

Authors: Joshua F. Nitsche, Alwin G. P. Schuller, Michael A. King, Min Zengh, Gavril W. Pasternak, John E. Pintar

Institutions: University of Medicine and Dentistry of New Jersey, Memorial Sloan Kettering Cancer Center

Language: English

Topic: Neuropeptides and Animal Physiology

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse