Dopamine receptor antagonist blocks the release of glycine, GABA, and taurine produced by amphetamine.
The effects of systemic injections of amphetamine sulfate on the extracellular levels of glycine, GABA, and taurine in the neostriatum of awake rats were studied using a push-pull perfusion system. Amphetamine produced a dose-related increase in glycine levels. Amphetamine also produced an enhancement on GABA and taurine levels, although these increases did not follow a dose-related curve. The percentage increase of amino acids produced by the highest dose of amphetamine (5 mg/kg) at the peak effect was: GLY 235.9%; GABA 218%, and TAU 177%. All these effects were blocked by the D1-D2 dopamine receptor antagonist, haloperidol. It is suggested that dopamine, released by amphetamine, induces the release of inhibitory amino acid neurotransmitters in the neostriatum. These results are consistent with the hypothesis of dopamine playing a role of an amplifier of the activity of different neurochemical circuits. The results are also in accord with the idea that dopamine could mediate the neurotoxic effects produced by amphetamines through an interplay between excitatory and inhibitory amino acids.
Porras
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A
Department of Human Physiology, Faculty of Medicine, University Complutense of Madrid, Spain.
Mora
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F
D000661:Amphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018492:Dopamine Antagonists; D013654:Taurine; D005680:gamma-Aminobutyric Acid; D000661:Amphetamine; D006220:Haloperidol; D005998:Glycine