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Operant Sensation Seeking in the Mouse
Published on: November 10, 2010
Brain mu and delta opioid receptors mediate different locomotor hyperactivity responses of the C57BL/6J mouse
G A Mickley1, M A Mulvihill, M A Postler
1Behavioral Sciences Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814-5145.
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.
Insights
Morphine, mu, and delta opioid receptor agonists all cause locomotor hyperactivity in mice. However, selective mu and delta agonists produce different behavioral patterns, indicating distinct roles in opioid-induced locomotion.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
- Opioid Receptor Research
Background:
- Morphine, a primary mu-opioid receptor agonist, also interacts with delta sites.
- The specific opioid receptor subtypes mediating morphine-induced locomotor hyperactivity remain unclear.
- Understanding these mechanisms is crucial for developing targeted pain management therapies.
Purpose of the Study:
- To investigate the neuropharmacology of opioid-induced locomotion in C57BL/6J mice.
- To differentiate the roles of mu and delta opioid receptors in mediating locomotor activity.
- To analyze qualitative differences in locomotor behavior induced by selective agonists.
Main Methods:
- Intraventricular administration of selective mu (DAGO) and delta (DPDPE) opioid receptor agonists, and morphine sulfate in male C57BL/6J mice.
- Utilized a sophisticated apparatus to measure various locomotor parameters.
- Injections were administered bilaterally into the lateral ventricles in a randomized order with sufficient washout periods.
Main Results:
- DAGO, DPDPE, and morphine all induced horizontal locomotor hyperactivity and increased the average distance per move.
- Morphine and DAGO significantly reduced vertical activity (rearing) and induced thigmotaxis (wall-hugging).
- DPDPE administration resulted in locomotor parameters similar to control mice, with no significant reduction in rearing or induction of thigmotaxis.
Conclusions:
- Both mu and delta opioid receptor agonists can induce locomotor hyperactivity in mice.
- Selective mu and delta receptor activation leads to distinct qualitative differences in locomotor topography.
- These findings suggest that both receptor subtypes play a role in opioid-induced locomotion, but through different behavioral pathways.
