Hypophysectomy may non-selectively alter pharmacokinetic parameters to enhance the ability of haloperidol to increase striatal dopamine receptor density in the rat |
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| Authors: | M D Simpson P Jenner C D Marsden |
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| Affiliation: | 1. School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China;2. School of Athletic Performance, Shanghai University of Sport, Shanghai 200438, China;1. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA;2. Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA;3. Department of Anesthesiology, Northwestern Memorial Hospital, Feinberg School of Medicine, Chicago, Illinois, USA;1. Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada;2. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland;3. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland;4. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland;5. Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland;6. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;1. Institute of Medical Science, University of Toronto, Toronto, ON, Canada;2. Division of Neurosurgery and Spine Program, Department of Surgery, University of Toronto, Toronto, ON, Canada;3. Division of Genetics and Development, Krembil Brain Institute, University Health Network, Toronto, ON, Canada;4. University of Toronto, Toronto, ON, Canada;5. Robert Campeau Foundation/Dr. C.H. Tator Chair in Brain and Spinal Cord Research at UHN, Toronto, ON, Canada;6. Krembil Brain Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada |
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| Abstract: | We have investigated the effect of a range of doses of haloperidol (0.625-5.0 mg/kg/day) or saline, administered for 14 days, followed by a 3 day drug washout period, to sham operated or hypophysectomized rats. Haloperidol increased the number of specific striatal 3H-spiperone binding sites (Bmax) in sham-operated animals at doses of 2.5 and 5.0 mg/kg/day, and in hypophysectomized animals at all doses used (0.625-5.0 mg/kg/day). The inhibition of locomotor activity produced by haloperidol was greater in hypophysectomized than sham-operated animals. Plasma and striatal haloperidol levels after equivalent doses were greater in hypophysectomized than in sham-operated animals. We conclude that hypophysectomy may enhance the ability of haloperidol to induce striatal dopamine receptor supersensitivity in the rat, and that this may be due to differences in the pharmacokinetic handling of haloperidol between sham-operated and hypophysectomized animals. |
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