INCREASES IN EXTRACELLULAR DOPAMINE LEVELS AND LOCOMOTOR-ACTIVITY AFTER DIRECT INFUSION OF PHENCYCLIDINE INTO THE NUCLEUS-ACCUMBENS

Three studies were conducted to provide a further characterization of the neurochemical and behavioral effects of phencyclidine (PCP). The first experiment utilized in vivo microdialysis to measure extracellular levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens. Administration of PCP (4.0 x 10(-4) M) in the dialysis perfusion medium produced large increases in extracellular DA, and biphasic changes in DOPAC. In the second experiment, chronic indwelling cannulae for drug infusion were implanted bilaterally into the nucleus accumbens. Local infusions of PCP (15.0, 30.0 or 60.0-mu-g per side) produced substantial increases in locomotor activity. Little or no headweaving, stereotypy or ataxia was observed after intra-accumbens injections of PCP. In the third experiment, systemic administration of 0.4 mg/kg haloperidol significantly reduced the locomotor activity induced by intra-accumbens injection of 15.0-mu-g PCP. These results indicate that PCP can increase extracellular levels of DA by direct actions in the DA terminal region, and that these effects are related to some of the behavioral stimulant properties of PCP.