title: Interactions between estradiol and haloperidol on perseveration and reversal learning in amphetamine-sensitized female rats.
abstract: There are sex differences associated with schizophrenia, as women exhibit later onset of the disorder, less severe symptomatology, and better response to antipsychotic medications. Estrogens are thought to play a role in these sex differences; estrogens facilitate the effects of antipsychotic medications to reduce the positive symptoms of schizophrenia, but it remains unclear whether estrogens protect against the cognitive symptoms of this disorder. Amphetamine sensitization is used to model some symptoms of schizophrenia in rats, including cognitive deficits like excessive perseveration and slower reversal learning. In this experiment female rats were administered a sensitizing regimen of amphetamine to mimic these cognitive symptoms. They were ovariectomized and administered either low or high estradiol replacement as well as chronic administration of the antipsychotic haloperidol, and were assessed in tests of perseveration and reversal learning. Results of these experiments demonstrated that, in amphetamine-sensitized rats, estradiol alone does not affect perseveration or reversal learning. However, low estradiol facilitates a 0.25mg/day dose of haloperidol to reduce perseveration and improve reversal learning. Combined high estradiol and 0.25mg/day haloperidol has no effect on perseveration or reversal learning, but high estradiol facilitates the effects of 0.13mg/day haloperidol to reduce perseveration and improve reversal learning. Thus, in amphetamine-sensitized female rats, 0.25mg/day haloperidol only improved perseveration and reversal learning when estradiol was low, while 0.13mg/day haloperidol only improved these cognitive processes when estradiol was high. These findings suggest that estradiol facilitates the effects of haloperidol to improve perseveration and reversal learning in a dose-dependent manner.
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada. Electronic address: anne.almey@gmail.com.
authors.forename: Anne
authors.initials: A
authors.lastname: Almey
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada.
authors.forename: Lauren
authors.initials: L
authors.lastname: Arena
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada.
authors.forename: Joshua
authors.initials: J
authors.lastname: Oliel
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada. Electronic address: waqqas19@gmail.com.
authors.forename: Waqqas M
authors.initials: WM
authors.lastname: Shams
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada.
authors.forename: Nada
authors.initials: N
authors.lastname: Hafez
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Mancinelli
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada.
authors.forename: Lukas
authors.initials: L
authors.lastname: Henning
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada.
authors.forename: Aleks
authors.initials: A
authors.lastname: Tsanev
authors.affiliation: Centre for Studies in Behavioral Neurobiology (CSBN), Department of Psychology, Concordia University, Montreal, QC, Canada. Electronic address: wayne.brake@concordia.ca.
authors.forename: Wayne G
authors.initials: WG
authors.lastname: Brake
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D051381:Rats; D012193:Reversal Learning / Q000187:drug effects*; D012565:Schizophrenic Psychology; D013239:Stereotyped Behavior / Q000187:drug effects*
chemical_list: D004958:Estradiol; D000661:Amphetamine; D006220:Haloperidol
keywords: Antipsychotic; Estrogens; Schizophrenia; Set-shifting