Phencyclidine and (+)-MK-801-induced circling preference: correlation with monoamine levels in striatum of the rat brain.
Phencyclidine (PCP; angel dust) is a drug of abuse known to produce a behavioral state in humans resembling schizophrenia/psychosis. PCP is a noncompetitive NMDA receptor antagonist and produces a variety of behaviors in rats including circling. The behavioral effects of other noncompetitive NMDA receptor antagonists such as (+)-MK-801 are still being elucidated. Here, adult female rats were dosed with PCP (10 mg/kg, IP), or (+)-MK-801 (0.1 mg/kg, IP) and circling preference was recorded for 2 h before sacrifice to determine monoamine levels by HPLC/EC. Animals injected with PCP or (+)-MK-801 showed a preference to turn to the left (65% and 72%, respectively). PCP and (+)-MK-801 also produced a significant increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in whole striatum on both sides of the brain. Further dissection of the striatum into medioventral and dorsolateral regions revealed that HVA was increased bilaterally except in globus pallidus where we found significant increases in dopamine (DA), DOPAC, and HVA only on the left side after PCP and (+)-MK-801 administration. These data suggest that PCP and (+)-MK-801 produce a greater preference to turn left than right, a finding similar to that found in human psychosis. Furthermore, it is possible that this preference to turn toward the left hemispace is due to an asymmetry in dopamine function found in the globus pallidus after administration of PCP and similar drugs.
Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR 72079.
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Ali
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Newport
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Bracha
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016291:Dizocilpine Maleate / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D010622:Phencyclidine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012016:Reference Values; D013239:Stereotyped Behavior / Q000187:drug effects*
D015306:Biogenic Monoamines; D016194:Receptors, N-Methyl-D-Aspartate; D015102:3,4-Dihydroxyphenylacetic Acid; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D006719:Homovanillic Acid