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World class computing and information science research at Strathclyde...

The Strathprints institutional repository is a digital archive of University of Strathclyde's Open Access research outputs. Strathprints provides access to thousands of Open Access research papers by University of Strathclyde researchers, including by researchers from the Department of Computer & Information Sciences involved in mathematically structured programming, similarity and metric search, computer security, software systems, combinatronics and digital health.

The Department also includes the iSchool Research Group, which performs leading research into socio-technical phenomena and topics such as information retrieval and information seeking behaviour.

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Molecular components of tolerance to opiates in single hippocampal neurons

Bushell, T. and Endoh, T. and Simen, A.A. and Ren, D. and Bindokas, V.P. and Miller, R.J. (2002) Molecular components of tolerance to opiates in single hippocampal neurons. Molecular Pharmacology, 61 (1). pp. 55-64. ISSN 0026-895X

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Abstract

We examined the effect of acute and chronic opioid treatment on synaptic transmission and µ-opioid receptor (MOR) endocytosis in cultures of naïve rat hippocampal neurons. Opioid agonists that activate MOR inhibited synaptic transmission at inhibitory but not excitatory autapses. [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), morphine, and methadone were all effective at blocking inhibitory transmission. These same drugs also reduced the amplitude of voltage-dependent Ca2+ currents in inhibitory but not excitatory neurons. Chronic treatment with all three opioids reduced the subsequent effects of a challenge with either the same drug or one of the others in individual autaptic neurons. Chronic treatment with DAMGO or methadone produced internalization of enhanced yellow fluorescent protein-tagged MOR expressed in hippocampal neurons within hours, whereas morphine produced internalization much more slowly, even when accompanied by overexpression of beta -arrestin-2. We conclude that DAMGO, methadone, and morphine all produce tolerance in single hippocampal neurons. Morphine-induced tolerance does not necessarily seem to involve receptor endocytosis.