Abstract
Both dopamine (DA) agonists and NMDA antagonists produce prepulse inhibition (PPI) deficits in rats that model PPI deficits in schizophrenia patients. While DA agonist effects on PPI are reversed by acute treatment with either “typical” high-potency D2 DA antagonists or “atypical” antipsychotics, PPI deficits produced by phencyclidine (PCP) are preferentially reversed by acute treatment with “atypical” antipsychotics. Acute effects of antipsychotics may not accurately model the more clinically relevant effects of these drugs that emerge after several weeks of continuous treatment. In the present study, sustained treatment with haloperidol via subcutaneous minipumps blocked the PPI-disruptive effects of apomorphine and attenuated the PCP-induced disruption of PPI. Restoration of PPI in apomorphine-treated rats was evident within the first week of sustained haloperidol administration. A partial reversal of PCP effects on PPI did not develop until the second week of sustained haloperidol treatment, followed a fluctuating course, but remained significant into the seventh week of sustained haloperidol administration. The delayed emergence of anti-PCP effects of haloperidol suggests that the brain substrates responsible for the DAergic and NMDA regulation of PPI are differentially sensitive to acute and chronic effects of antipsychotics.
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Acknowledgements
This study was supported by MH01436 and MH53484 (NRS), DA02925 (MAG) and VA grant (MAG, ZAM), Department of Veterans Affairs VISN22 Mental Illness Research, Education and Clinical Center (MIRECC) The authors gratefully acknowledge the expert technical assistance of Mr. Navid Taaid and Ms. Pamela Auerbach.
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Martinez, Z., Oostwegel, J., Geyer, M. et al. “Early” and “Late” Effects of Sustained Haloperidol on Apomorphine- and Phencyclidine-induced Sensorimotor Gating Deficits. Neuropsychopharmacol 23, 517–527 (2000). https://doi.org/10.1016/S0893-133X(00)00147-0
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DOI: https://doi.org/10.1016/S0893-133X(00)00147-0
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