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Published on: February 18, 2016
Effects of postmethamphetamine treatment with restraint on ambulatory sensitization to methamphetamine in mice
1Department of Neurobiology and Behavior, Gunma University School of Medicine, Maebashi, Japan.
Abstract:
The administration of methamphetamine (2 mg/kg SC) to mice was followed by acceleration of ambulation (locomotion) for 3 h, with the peak effect at 1/2-1 h. When mice were allowed free ambulation for 3 h in an activity cage of 20 cm in diameter after methamphetamine administration, repeated administrations of methamphetamine, four times at 3-day intervals, caused ambulatory sensitization; the count at the fourth administration being approximately 2.3 times as high as that at the first administration. Furthermore, the mice that were allowed ambulation in the activity cage during postmethamphetamine period of either 0-1/2, 0-1, 0-2, or 1/2-1 h (during the other periods, the mice were put in jars of 6 cm in diameter to restrict ambulation) demonstrated ambulatory sensitization to methamphetamine, and these levels were as same as that in the mice given methamphetamine with free ambulation for 3 h. However, the free ambulation during postmethamphetamine periods of 0-1/4 h and 1-3 h failed to produce strong sensitization to methamphetamine. These results suggest that a free ambulation for at least 1/2 h during the postmethamphetamine period of 0-1 h is important for induction of ambulatory sensitization to methamphetamine in mice.
Insights
Free ambulation for at least 30 minutes within the first hour after methamphetamine administration is crucial for developing ambulatory sensitization in mice. This finding highlights the importance of environmental interaction in drug-induced behavioral changes.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Methamphetamine administration in mice accelerates ambulation (locomotion).
- Repeated methamphetamine exposure can lead to ambulatory sensitization, a phenomenon where the drug's effects intensify with subsequent doses.
Purpose of the Study:
- To investigate the critical period of post-administration ambulation required for inducing ambulatory sensitization to methamphetamine in mice.
- To determine the optimal duration and timing of free ambulation following methamphetamine exposure for sensitization development.
Main Methods:
- Mice received methamphetamine (2 mg/kg SC) and were allowed varying durations of free ambulation in an activity cage post-administration.
- Sensitization was assessed by comparing ambulation counts across repeated methamphetamine administrations.
- Control groups experienced restricted ambulation during specific post-administration intervals.
Main Results:
- Repeated methamphetamine administration (4 times at 3-day intervals) resulted in a 2.3-fold increase in ambulation, indicating sensitization.
- Free ambulation for at least 0.5 hours within the 0-1 hour post-methamphetamine period was sufficient to induce robust ambulatory sensitization.
- Periods of restricted ambulation or ambulation outside this critical window (e.g., 0-0.25h, 1-3h) failed to produce significant sensitization.
Conclusions:
- A specific window of opportunity exists for environmental stimuli, like free ambulation, to influence drug-induced behavioral plasticity.
- At least 30 minutes of free ambulation between 0 and 1 hour post-methamphetamine administration is essential for the induction of ambulatory sensitization.
- Environmental enrichment during critical post-drug periods plays a significant role in the development of behavioral sensitization to psychostimulants.
