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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Memory impairment and reduced exploratory behavior in mice after administration of systemic morphine
Junichi Kitanaka1, Nobue Kitanaka1, F Scott Hall2
1Department of Pharmacology, Hyogo College of Medicine, Hyogo, Japan.
Abstract:
In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg) or β-funaltrexamine (5 mg/kg) but not by norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the morphine-induced spatial memory impairment was mediated predominantly by μ-opioid receptors (MOPs). Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg) or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg), in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety.
Insights
Morphine impairs spatial memory and reduces exploratory behavior in mice, primarily through mu-opioid receptors (MOPs). These effects on memory and exploration are not linked to changes in locomotion or anxiety.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Opioid analgesics like morphine have complex effects on cognitive functions.
- Understanding the specific receptor pathways involved in morphine's cognitive effects is crucial.
Purpose of the Study:
- To investigate the impact of morphine on spatial memory, object exploration, locomotion, and anxiety in male ICR mice.
- To determine the specific opioid receptor subtypes mediating morphine-induced cognitive impairments.
Main Methods:
- Administration of morphine (15 or 30 mg/kg, i.p.) and various opioid receptor antagonists (naloxone, β-funaltrexamine, norbinaltorphimine, naltrindole).
- Assessment of spatial memory using the Y-maze and Morris water maze (MWM).
- Evaluation of object exploration, locomotion, and anxiety using novel-object exploration, open field, elevated plus maze, and marble-burying tests.
Main Results:
- Morphine significantly decreased Y-maze alternations, indicating spatial short-term memory impairment, which was blocked by naloxone and β-funaltrexamine, implicating mu-opioid receptors (MOPs).
- Spatial memory retrieval was impaired by morphine in the MWM.
- Morphine reduced exploratory behavior in the novel-object exploration test and decreased marble burying, suggesting altered exploratory drive, without affecting locomotion or anxiety levels.
Conclusions:
- Morphine induces significant impairments in spatial short-term memory and retrieval in mice.
- The observed cognitive deficits are predominantly mediated by mu-opioid receptors (MOPs).
- Morphine reduces exploratory behavior but does not alter general locomotion or anxiety-like behavior in this model.
