title: Sex differences in diazepam effects and parvalbumin-positive GABA neurons in trait anxiety Long Evans rats.
abstract: In clinical populations, prevalence rates for a number of anxiety disorders differ between males and females and gonadal hormones are thought to contribute to these differences. While these hormones have been shown to modulate the anxiolytic effects of the benzodiazepine agonist diazepam in some models, findings are inconsistent. Here, we tested for sex differences in response to anxiogenic stimuli following a 30-min diazepam (1.0mg/kg) pre-treatment in male and female rats showing high (HAn) and low (LAn) anxiety-like behavior on the elevated plus maze. Acute diazepam administration resulted in decreased anxiety-like behavior only in HAn males as demonstrated by a significant increase in percent open arm time in the elevated plus maze (EPM). Immunohistochemical analysis for parvalbumin (PV; a calcium-binding protein that selectively stains GABAergic neurons) in central amygdala (CeA), caudate putamen (CPu) and the hippocampus indicated the number of GABAergic interneurons in these areas differed across sex and anxiety trait. In the CPu, females had significantly more PV-immunoreactive (IR) cells than males, and LAn females had greater PV-IR neurons than HAn females. In the CeA, males displayed an increased number of PV-IR neurons compared to females, with no differences found between LAn and HAn. Further, trait differences were evident in the CA2 region of the hippocampus, regardless of sex. Taken together, these data suggest that gonadal hormones and trait anxiety may influence the sensitivity to the anti-anxiety effects of diazepam and these differences may be due in part to the distribution of GABA-containing interneurons.
authors.affiliation: Department of Biological Sciences, Fordham University, Rose Hill Campus, Bronx, NY 10458, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ravenelle
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University, Feinberg School of Medicine, 303 E Chicago Avenue, #12-104, Chicago, IL 60611, USA.
authors.forename: Nichole M
authors.initials: NM
authors.lastname: Neugebauer
authors.affiliation: Developmental and Brain Sciences, Department of Psychology, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Niedzielak
authors.affiliation: Developmental and Brain Sciences, Department of Psychology, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA. Electronic address: Tiffany.Donaldson@umb.edu.
authors.forename: S Tiffany
authors.initials: ST
authors.lastname: Donaldson
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010320:Parvalbumins / Q000737:chemistry; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors
chemical_list: D014151:Anti-Anxiety Agents; D010320:Parvalbumins; D003975:Diazepam
keywords: Amygdala; Anxiety; Diazepam; Elevated plus maze; GABA; Striatum