Haloperidol given chronically decreases basal dopamine in the prefrontal cortex more than the striatum or nucleus...

Simultaneous microdialysis was performed in the prefrontal cortex, striatum, and the caudal region of the nucleus accumbens using implanted guide shafts with removable microdialysis probes. Extracellular dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured in response to acute and chronic haloperidol, an antipsychotic drug. Six rats received haloperidol (0.5 mg/kg, IP) while changes in DA and its metabolites were monitored for six hours. Then the microdialysis probes were removed and daily injections of haloperidol were given for 28 more days. Next the probes were reinserted, and a final haloperidol challenge was given. A control group of six rats was treated the same way but with saline. The first injection of haloperidol increased extracellular DA, DOPAC and HVA proving increased turnover in all three regions. A month later, after chronic treatment, basal DA and its metabolites decreased in just the cortex. DOPAC and HVA also decreased in the cortex and striatum, suggesting a decrease in turnover at these two sites. None of these changes occurred in the accumbens. The last haloperidol challenge after chronic treatment no longer increased extracellular DA in any of the three sites, but increased production of metabolites was still detectable. This suggests a lack of DA responsiveness in all three sites. In summary, chronic haloperidol affected each of the regions differently; DA metabolites decreased in the STR and PFC; basal DA decreased in the PFC.