Reduced prefrontal cortical dopamine, but not acetylcholine, release in vivo after repeated, intermittent phencyclidine administration to rats.
Subchronic administration of phencyclidine to rats or monkeys produces prefrontal cortical cognitive dysfunction, as well as reduced frontal cortical dopamine utilization. In the current study, the effects of subchronic exposure to phencyclidine on dopamine and acetylcholine release in the prefrontal cortex were assessed, using in vivo microdialysis in conscious rats. Subchronic exposure to phencyclidine (5 mg/kg twice daily for 7 days) reduced both basal extracellular concentrations of dopamine as well as the increase in dopamine release produced by an acute phencyclidine challenge. The increase in dopamine release induced by a high potassium concentration in the perfusate tended to be reduced after subchronic phencyclidine treatment, while basal and evoked acetylcholine release was unaffected. These data demonstrate that altered dopamine turnover in subjects after subchronic exposure to phencyclidine is directly reflective of reduced release, and as such, represents a functionally relevant phenomenon.
Jentsch
J D
JD
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA.
Dazzi
L
L
Chhatwal
J P
JP
Verrico
C D
CD
Roth
R H
RH
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D010622:Phencyclidine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D010622:Phencyclidine; D000109:Acetylcholine; D004298:Dopamine