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Brain μ and δ opioid receptors mediate different locomotor hyperactivity responses of the C57BL/6J mouse

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Abstract

Morphine induces a dose-dependent stereotypic locomotor hyperactivity in the C57BL/6J mouse. Although morphine is the prototypical opioid μ receptor agonist, it also binds at δ sites. This has led to speculation as to which set(s) of receptor subtypes mediate opiate-induced locomotor hyperactivity. Here we use selective μ and δ receptor agonists as well as a sophisticated activity measuring apparatus to investigate the neuropharmacology of opioid-induced locomotion in the mouse. Male C57BL/6J mice were implanted with chronic bilateral cannula aimed at the lateral ventricles. Following recovery from surgery, mice received a series of bilateral 1 µl intraventricular (i.vent.) injections of [D-Ala2-MePhe4-Glyol5] enkephalin (DAGO) (0.1, 1.0, 2.0 µg), [D-Pen2, D-Pen5] enkephalin (DPDPE) (2.5, 5.0, 10.0, 30.0 µg) (compounds with respective μ and δ opioid receptor selectivity), morphine sulfate (10.0, 20.0, 60.0 µg), or saline. Injections were separated by at least 3 days and were presented in a randomized order. We measured several locomotor parameters following each injection. DAGO, DPDPE and morphine each produced horizontal locomotor hyperactivity and lengthened the average distance per move. While morphine and DAGO significantly reduced vertical activity (rearing) and produced thigmotaxis (wall-hugging), DPDPE-injected mice were similar to controls on these locomotor parameters. These data reveal that mouse locomotor hyperactivity can be observed following injections of either morphine or more-selective opioid μ or δ receptor agonists. However, within the drug/dose regimens used here, we noticed qualitative differences in the locomotor topography produced by the selective μ and δ receptor agonists.

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Andrew Mickley, G., Mulvihill, M.A. & Postler, M.A. Brain μ and δ opioid receptors mediate different locomotor hyperactivity responses of the C57BL/6J mouse. Psychopharmacology 101, 332–337 (1990). https://doi.org/10.1007/BF02244050

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  • DOI: https://doi.org/10.1007/BF02244050

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