title: High estrogen and chronic haloperidol lead to greater amphetamine-induced BOLD activation in awake, amphetamine-sensitized female rats.
abstract: The ovarian hormone estrogen has been implicated in schizophrenia symptomatology. Low levels of estrogen are associated with an increase in symptom severity, while exogenous estrogen increases the efficacy of antipsychotic medication, pointing at a possible interaction between estrogen and the dopaminergic system. The aim of this study is to further investigate this interaction in an animal model of some aspects of schizophrenia using awake functional magnetic resonance imaging. Animals receiving 17β-estradiol and haloperidol were scanned and BOLD activity was assessed in response to amphetamine. High 17β-estradiol replacement and chronic haloperidol treatment showed increased BOLD activity in regions of interest and neural networks associated with schizophrenia (hippocampal formations, habenula, amygdala, hypothalamus etc.), compared with low, or no 17β-estradiol. These data show that chronic haloperidol treatment has a sensitizing effect, possibly on the dopaminergic system, and this effect is dependent on hormonal status, with high 17β-estradiol showing the greatest BOLD increase. Furthermore, these experiments further support the use of imaging techniques in studying schizophrenia, as modeled in the rat, but can be extended to addiction and other disorders.
authors.affiliation: Concordia University, Department of Psychology, Center for Studies in Behavioural Neurobiology, 7141 Sherbrooke St. West, Montreal, QC, Canada, H4B 1R6. Electronic address: dan.madularu@gmail.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Madularu
authors.affiliation: Northeastern University, Department of Psychology, Center for Translational Neuroimaging, 360 Huntington Ave, Boston, MA, USA, 02115.
authors.forename: Praveen
authors.initials: P
authors.lastname: Kulkarni
authors.affiliation: Northeastern University, Department of Psychology, Center for Translational Neuroimaging, 360 Huntington Ave, Boston, MA, USA, 02115.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Yee
authors.affiliation: Northeastern University, Department of Psychology, Center for Translational Neuroimaging, 360 Huntington Ave, Boston, MA, USA, 02115.
authors.forename: William M
authors.initials: WM
authors.lastname: Kenkel
authors.affiliation: Concordia University, Department of Psychology, Center for Studies in Behavioural Neurobiology, 7141 Sherbrooke St. West, Montreal, QC, Canada, H4B 1R6.
authors.forename: Waqqas M
authors.initials: WM
authors.lastname: Shams
authors.affiliation: Northeastern University, Department of Psychology, Center for Translational Neuroimaging, 360 Huntington Ave, Boston, MA, USA, 02115.
authors.forename: Craig F
authors.initials: CF
authors.lastname: Ferris
authors.affiliation: Concordia University, Department of Psychology, Center for Studies in Behavioural Neurobiology, 7141 Sherbrooke St. West, Montreal, QC, Canada, H4B 1R6.
authors.forename: Wayne G
authors.initials: WG
authors.lastname: Brake
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D010052:Ovariectomy; D010100:Oxygen / Q000097:blood* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D004958:Estradiol; D000661:Amphetamine; D006220:Haloperidol; D010100:Oxygen; D004298:Dopamine
keywords: Antipsychotic; Dopamine; Estradiol; Ovariectomy; Schizophrenia; fMRI