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No tolerance to antiaggressive effect of d-amphetamine in mice
Abstract:
Agonistic, locomotor, and stereotyped behavior were measured in male Swiss-Webster mice in their home cage, normally shared with a female, while confronting an intruder mouse. Acute administration of d-amphetamine (2, 4, 8 mg/kg, IP) to resident mice decreased the frequency of attacks toward an untreated intruder, increased the resident's locomotor activity, and induced a small amount of stereotyped behavior. Redetermination of dose-effect functions during chronic treatment (8 or 16 mg/kg/day) indicated that tolerance did not develop to the antiaggressive effect of d-amphetamine. By contrast, the chronically treated mice showed sensitization to amphetamine-induced stereotypies and a diminished sensitivity to the drug's enhancement of locomotor activity. Subsequent tests with cocaine indicated no differences between amphetamine-maintained and saline control animals, providing no evidence for cross-tolerance or cross-sensitization between cocaine's and amphetamine's effects on attack, locomotion, and stereotypies.
Insights
d-amphetamine reduces aggression in mice but causes tolerance to locomotor effects and sensitization to stereotypies with chronic use. No cross-tolerance or sensitization was observed with cocaine.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Behavior
Background:
- Aggression, locomotion, and stereotyped behaviors are key indicators of drug effects in animal models.
- d-amphetamine is a psychostimulant known to affect various behavioral domains.
Purpose of the Study:
- To investigate the effects of acute and chronic d-amphetamine administration on agonistic, locomotor, and stereotyped behaviors in male mice.
- To examine potential tolerance or sensitization to d-amphetamine's behavioral effects with repeated administration.
- To assess cross-tolerance or cross-sensitization between d-amphetamine and cocaine.
Main Methods:
- Male Swiss-Webster mice were administered acute doses of d-amphetamine (2-8 mg/kg) or chronic doses (8-16 mg/kg/day).
- Behaviors including attacks, locomotion, and stereotypies were measured during resident-intruder interactions.
- Subsequent tests involved cocaine administration to assess cross-effects.
Main Results:
- Acute d-amphetamine decreased attack frequency, increased locomotion, and induced mild stereotypies.
- Chronic treatment showed no tolerance to the anti-aggressive effect but developed tolerance to locomotor enhancement.
- Sensitization occurred for amphetamine-induced stereotypies; no cross-tolerance or sensitization was found with cocaine.
Conclusions:
- d-amphetamine exhibits distinct acute and chronic effects on mouse behavior, with tolerance developing to some effects but not others.
- The findings suggest differential neuroadaptations to chronic d-amphetamine exposure.
- No evidence of cross-tolerance or cross-sensitization between d-amphetamine and cocaine was observed in these behavioral paradigms.