title: Differential effect of amphetamine on c-fos expression in female aromatase knockout (ArKO) mice compared to wildtype controls.
abstract: Estrogen may be involved in psychosis by an interaction with central dopaminergic activity. Aromatase knockout mice are unable to produce estrogen and have been shown to display altered behavioural responses and effects of the dopamine releaser, amphetamine. This study investigates the effect of gonadal status on amphetamine-induced c-fos expression in the brains of female aromatase knockout and wildtype mice. Six groups of mice were treated intraperitoneally with saline or 5mg/kg amphetamine. Fos immunoreactivity was assessed in the cingulate cortex, caudate putamen and nucleus accumbens. Aromatase knockout mice showed markedly reduced amphetamine-induced Fos immunoreactivity compared to wildtype mice. However, the amphetamine response was restored in aromatase-knockout mice after ovariectomy, which reduced this effect in wildtype controls. Estrogen supplementation reversed the effect of ovariectomy in wildtype mice but had no additional significant effect in aromatase-knockout mice. These results indicate that mechanisms involved in amphetamine-induced c-fos expression are altered in aromatase knockout mice and that the primary hormone involved in this effect is not estrogen, but may be another factor released from the ovaries, such as an androgen. These results provide new insight into the effect of gonadal hormones on amphetamine induced c-fos expression in this mouse model of estrogen deficiency. These results could be important for our understanding of the role of sex steroid hormones in psychosis.
authors.affiliation: Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Parkville, Melbourne, Australia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Chavez
authors.forename: Andrea
authors.initials: A
authors.lastname: Gogos
authors.forename: Rachel
authors.initials: R
authors.lastname: Hill
authors.forename: Michelle
authors.initials: M
authors.lastname: Van Sinderen
authors.forename: Evan
authors.initials: E
authors.lastname: Simpson
authors.forename: Wah Chin
authors.initials: WC
authors.lastname: Boon
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000235:genetics*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D010052:Ovariectomy
chemical_list: D000661:Amphetamine; D001141:Aromatase