title: Amygdalar activation of group I metabotropic glutamate receptors produces anti- and pro-conflict effects depending upon animal sex in a sexually dimorphic conditioned conflict-based anxiety model.
abstract: Women are more susceptible than men to develop anxiety disorders, however, the mechanisms involved are still unclear. In this study, we investigated the role of group I metabotropic glutamate receptors (mGluRs), a target for anxiety disorders, and whether estradiol may modulate conflict-based anxiety in female rats by using the Vogel Conflict Test (VCT). We used ovariectomized female rats with high (OVX+EB) and low (OVX) estradiol levels and intact male rats to evaluate sex differences. Infusion of (S)-3,5-Dihydroxyphenylglycine (DHPG), a group I mGluR agonist, into the basolateral amygdala, a region involved in anxiety-responses, statistically increased the number of shocks in OVX, but not OVX+EB female rats at 0.1, nor at 1.0 μM. In contrast, DHPG statistically decreased the number of shocks in male rats at 1.0 μM only. DHPG (0.1 μM) increased the number of recoveries in OVX, but not OVX+EB or male rats. Sex differences were detected for the number of shocks, recoveries and punished licks, where female rats displayed more conflict than male rats. Western blot analyses showed that protein expression of mGluR1, but not mGluR5 was higher in OVX+EB>OVX>male rats in the amygdala, whereas no significant differences were detected in the hippocampus, olfactory bulb and/or the periaqueductal gray. Therefore, DHPG produced paradoxical effects that are sex dependent; producing anxiolytic-like effects in female rats, while anxiogenic-like effects in male rats according to the VCT. These results highlight the importance of including female experimental models to underpin the neural circuitry of anxiety according to sex and for the screening of novel anxiolytic compounds.
authors.affiliation: Department of Biology, University of Puerto Rico, Cayey Campus, PO Box 372230, Cayey, PR 00737-2230, USA.
authors.forename: María I
authors.initials: MI
authors.lastname: De Jesús-Burgos
authors.affiliation: Department of Biology, University of Puerto Rico, Río Piedras Campus, San Juan, PR 00931, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: González-García
authors.affiliation: Department of Social Sciences, University of Puerto Rico, Cayey Campus, PO Box 372230, Cayey, PR 00737-2230, USA.
authors.forename: Yanira
authors.initials: Y
authors.lastname: Cruz-Santa
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, UPR-MSC, PO Box 365067, San Juan, PR 00936-5067, USA. Electronic address: nivia.perez@upr.edu.
authors.forename: Nivia L
authors.initials: NL
authors.lastname: Pérez-Acevedo
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000473:pathology* / Q000523:psychology*; D002047:Buprenorphine / Q000494:pharmacology / Q000627:therapeutic use; D003213:Conditioning, Psychological / Q000187:drug effects; D003220:Conflict, Psychological; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000627:therapeutic use; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D014151:Anti-Anxiety Agents; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D002047:Buprenorphine; D004958:Estradiol; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol
keywords: Basolateral amygdala; Estradiol; Group I metabotropic glutamate receptos; Sex differences; Vogel Conflict Test