Alterations in striatal dopamine overflow during rotational behavior induced by amphetamine, phencyclidine, and MK-801.
Rats lesioned unilaterally in the medial forebrain bundle with 6-OHDA rotated ipsilateral to the lesion following injections of amphetamine, phencyclidine (PCP), and MK-801. Concurrent measurement of striatal dopamine (DA) in the intact striatum with in vivo microdialysis revealed a dissociation between rotational behavior and alterations in DA overflow induced by the three drugs. Amphetamine produced robust ipsilateral rotational behavior and a substantial elevation in striatal DA (approximately 130% increase at asymptote). PCP produced comparable increases in rotational behavior, but only approximately 30% increase in striatal DA. MK-801 also had a comparable behavioral effect but failed to alter DA overflow in the intact striatum. Since MK-801, a noncompetitive NMDA antagonist which does not enhance extracellular dopamine in the striatum, is able to produce ipsilateral rotational behavior in rats with unilateral nigrostriatal lesions, it is likely that the effects of PCP may also be determined predominantly through NMDA blockade in this model.
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Biological Psychiatry Branch, National Institute of Mental Health, NIH, Bethesda, Maryland 20892-1272, USA.
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D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000378:metabolism*; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D000661:Amphetamine; D010622:Phencyclidine; D004298:Dopamine