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Early post-treatment with haloperidol retards induction of methamphetamine sensitization in mice
1Department of Neurobiology and Behavior, Gunma University School of Medicine, Maebashi, Japan.
Abstract:
The repeated administration of methamphetamine (2 mg/kg s.c.) at 3- to 4-day intervals induced sensitization to its ambulation-increasing effect in mice. When the simultaneous administration of methamphetamine with haloperidol (0.025, 0.1 and 0.4 mg/kg s.c.) was carried out, the acute ambulation-increasing effect as well as the development of sensitization were haloperidol-dose-dependently inhibited. Moreover, treatment with haloperidol (0.1 and 0.4 mg/kg) 3 h following each methamphetamine administration, which per se did not affect the acute ambulation increase caused by methamphetamine, could protect against the induction of methamphetamine sensitization in a dose-dependent manner, whereas treatment with haloperidol after 24 h did not show such protective action. The present results suggest that blockade of the dopamine receptors at an early period following each administration of methamphetamine may be responsible for the delay in development of methamphetamine sensitization as expressed by ambulatory activity of mice.
Insights
Repeated methamphetamine administration causes increased movement in mice. Co-administering haloperidol, a dopamine receptor blocker, dose-dependently inhibited this effect and prevented sensitization.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Methamphetamine (MAP) is a psychostimulant known to induce behavioral sensitization.
- Dopamine receptor blockade is a potential mechanism to modulate MAP-induced effects.
Purpose of the Study:
- To investigate the effect of haloperidol on methamphetamine-induced ambulation and sensitization in mice.
- To determine the role of dopamine receptor blockade timing in preventing MAP sensitization.
Main Methods:
- Mice received repeated subcutaneous injections of methamphetamine (2 mg/kg) at 3- to 4-day intervals.
- Haloperidol (0.025, 0.1, 0.4 mg/kg) was administered simultaneously with or 3 hours/24 hours after methamphetamine.
- Ambulatory activity was measured to assess acute effects and sensitization development.
Main Results:
- Simultaneous administration of haloperidol dose-dependently inhibited the acute ambulation-increasing effect of methamphetamine.
- Haloperidol also dose-dependently inhibited the development of methamphetamine-induced sensitization.
- Treatment with haloperidol 3 hours post-methamphetamine, but not 24 hours post-, protected against sensitization induction.
Conclusions:
- Early blockade of dopamine receptors following methamphetamine administration is crucial for preventing the development of behavioral sensitization.
- These findings suggest a critical time window for dopamine receptor involvement in MAP sensitization.