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D-alanine inhibits methamphetamine-induced hyperactivity in rats.

A Hashimoto1, T Nishikawa, T Oka

  • 1Division of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

European Journal of Pharmacology
|September 4, 1991
PubMed
Summary

D-alanine, but not L-alanine, reduced methamphetamine-induced hyperactivity in rats. This suggests that modulating excitatory amino acid neurotransmission may be a strategy for managing stimulant-induced behavioral changes.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Neurochemistry

Background:

  • Methamphetamine is a stimulant known to induce hyperactivity.
  • Excitatory amino acids, such as glycine, play a role in neurotransmission within the central nervous system.
  • The N-methyl-D-aspartate (NMDA) receptor complex is involved in synaptic plasticity and neurotransmission.

Purpose of the Study:

  • To investigate the role of D-alanine and L-alanine in modulating methamphetamine-induced locomotor stimulation in rats.
  • To explore the potential involvement of the NMDA receptor complex and its glycine binding site in methamphetamine's behavioral effects.

Main Methods:

  • Rats received bilateral intracerebroventricular injections of D-alanine or L-alanine.
  • Methamphetamine was administered subcutaneously to induce locomotor stimulation.

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  • Locomotor activity was measured to assess the effects of alanine administration.

    • Main Results:

    • D-alanine (200-600 micrograms/rat) significantly antagonized methamphetamine-induced locomotor stimulation.
    • L-alanine (600 micrograms/rat) did not affect the locomotor stimulation induced by methamphetamine.
    • The stereoselective antagonism by D-alanine suggests a role for the strychnine-insensitive glycine binding site of the NMDA receptor.

    Conclusions:

    • Reduced excitatory amino acidergic neurotransmission may be implicated in methamphetamine-induced hyperactivity.
    • D-alanine's antagonism suggests a potential therapeutic target for managing stimulant-induced hyperactivity by modulating NMDA receptor function.