TY - JOUR T1 - Phencyclidine Increases Forebrain Monoamine Metabolism in Rats and Monkeys: Modulation by the Isomers of HA966 JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1769 LP - 1775 DO - 10.1523/JNEUROSCI.17-05-01769.1997 VL - 17 IS - 5 AU - J. David Jentsch AU - John D. Elsworth AU - D. Eugene Redmond Jr. AU - Robert H. Roth Y1 - 1997/03/01 UR - http://www.jneurosci.org/content/17/5/1769.abstract N2 - The noncompetitive NMDA receptor antagonist phencyclidine (PCP) has psychotomimetic properties in humans and activates the frontal cortical dopamine innervation in rats, findings that have contributed to a hyperdopaminergic hypothesis of schizophrenia. In the present studies, the effects of the enantiomers of 3-amino-1-hydroxypyrrolid-2-one (HA966) on PCP-induced changes in monoamine metabolism in the forebrain of rats and monkeys were examined, because HA966 has been shown previously to attenuate stress- or drug-induced activation of dopamine systems. In rats, PCP (10 mg/kg, i.p.) potently activated dopamine (DA) turnover in the medial prefrontal cortex (PFC) and nucleus accumbens. Serotonin utilization was also increased in PFC. Pretreatment with either R-(+)HA966 (15 mg/kg, i.p.) or S-(−)HA966 (3 mg/kg, i.p.) partially blocked PCP-induced increases in PFC DA turnover, whereas neither enantiomer altered the effect of PCP on DA turnover in the nucleus accumbens or the PCP-induced increases in serotonin turnover in PFC. PCP (0.3 mg/kg, i.m.) exerted regionally selective effects on the dopaminergic and serotonergic innervation of the monkey frontal cortex, effects blocked by pretreatment with S-(−)HA966 (3 mg/kg, i.m.). Importantly, these data demonstrate that in the primate, PCP has potent effects on dopamine transmission in the frontal cortex, a brain region thought to be dysfunctional in schizophrenia. In addition, a role for S-(−)HA966 as a modulator of cortical monoamine transmission in primates is posited. ER -