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

Abstract

Morphine induces a dose-dependent stereotypic locomotor hyperactivity in the C57BL/6J mouse. Although morphine is the prototypical opioid mu receptor agonist, it also binds at delta sites. This has led to speculation as to which set(s) of receptor subtypes mediate opiate-induced locomotor hyperactivity. Here we use selective mu and delta 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 microliter intraventricular (i.vent.) injections of [D-Ala2-MePhe4-Glyol5]enkephalin (DAGO) (0.1, 1.0, 2.0 micrograms), [D-Pen2, D-Pen5] enkephalin (DPDPE) (2.5, 5.0, 10.0, 30.0 micrograms) (compounds with respective mu and delta opioid receptor selectivity), morphine sulfate (10.0, 20.0, 60.0 micrograms), 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 mu or delta receptor agonists. However, within the drug/dose regimens used here, we noticed qualitative differences in the locomotor topography produced by the selective mu and delta receptor agonists.