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Heightened aggressive behavior during morphine withdrawal: effects of d-amphetamine
1Department of Psychology, Tufts University, Medford, MA 02155.
Abstract:
The morphine withdrawal syndrome is composed of profound short- and long-term changes in autonomic, somato-motor and affective functions. In mice, morphine withdrawal produces heightened aggressive behavior and alterations in motor behavior; however, it is unclear whether these changes in behavior occur in unison and are dependent on a common mechanism or occur independently. In order to characterize the morphine withdrawal syndrome in mice, male Swiss-Webster mice were housed with female partners for 3-4 weeks before being implanted subcutaneously with morphine or placebo pellets. The pellets were removed 72 h after implantation and behavioral measurements were conducted 5, 48 and 96 h after pellet removal. During these tests, mice received d-amphetamine (0.3-10 mg/kg) or saline after which they were assessed for changes in motor behavior and for changes in aggressive behavior while confronting a group-housed male "intruder". In morphine-withdrawn mice, frequency of attack behavior was increased by approximately 30% and this effect persisted for at least 4 days. In contrast, explosive jumping was increased and walking and rearing were greatly decreased at the onset of the withdrawal period but declined within the first 24 h and returned to control levels within 48 h of pellet removal. d-Amphetamine maintained the elevated level of aggressive behavior and sharply increased locomotion in morphine-withdrawn mice; in placebo-pelleted mice, d-amphetamine dose-dependently decreased aggressive behaviors while increasing locomotion. The differential time course and the differential modification by d-amphetamine suggest that heightened aggressive behavior is a long-lasting consequence of morphine-withdrawal based on separate mechanisms than the short-lived alterations in motor activity.
Insights
Morphine withdrawal in mice causes long-lasting aggression and short-term motor changes. These behaviors stem from different underlying mechanisms, as shown by their distinct recovery times and responses to d-amphetamine.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Addiction Research
Background:
- Morphine withdrawal syndrome involves complex autonomic, motor, and affective changes.
- Previous studies in mice noted heightened aggression and motor alterations during morphine withdrawal, but their relationship was unclear.
Purpose of the Study:
- To characterize the morphine withdrawal syndrome in mice.
- To investigate the relationship between aggressive and motor behaviors during withdrawal.
- To determine if these behavioral changes are mediated by common or independent mechanisms.
Main Methods:
- Male Swiss-Webster mice received morphine or placebo pellets, followed by pellet removal and behavioral assessments at 5, 48, and 96 hours.
- Mice were challenged with d-amphetamine or saline to assess motor and aggressive behaviors.
- Aggressive behavior was measured by confronting withdrawn mice with an intruder.
Main Results:
- Morphine withdrawal significantly increased attack behavior frequency by ~30% for at least 4 days.
- Motor alterations (explosive jumping, decreased walking/rearing) were prominent early but resolved within 48 hours.
- d-Amphetamine sustained aggression in withdrawn mice but decreased it in controls, while increasing locomotion in both groups.
Conclusions:
- Heightened aggressive behavior is a long-lasting consequence of morphine withdrawal.
- Short-lived motor activity changes during withdrawal are mediated by different mechanisms than aggression.
- These findings suggest distinct neurobiological pathways underlie the affective and motor components of morphine withdrawal.