1. ¹Department of Psychology, Research – The University at Albany – Suny, Albany, NY, USA
2. ²Instituto Cajal, C.S.I.C., Madrid, Spain
3. ³Department of Biological Sciences, Research – The University at Albany – Suny, Albany, NY, USA
4. ⁴The Centers for Neuroscience, Research – The University at Albany – Suny, Albany, NY, USA
5. ⁵Department of Life Sciences, Research – The University at Albany – Suny, Albany, NY, USA

Correspondence: Dr CA Frye, Department of Psychology, The University at Albany-SUNY, Life Sciences Research Building 01058, 1400 Washington Avenue, Albany, NY 12222, USA. Tel: +1 518 591 8839, Fax: +1518 591 8848, E-mail: cafrye@albany.edu

Received 2 October 2006; Revised 7 February 2007; Accepted 7 March 2007; Published online 18 April 2007.

Abstract

Estradiol (E₂) modulates affective and socio-sexual behavior of female rodents. E₂'s functional effects may involve actions through and isoforms of estrogen receptor (ERs). The importance of E₂'s actions at these isoforms for anxiety (open field, elevated plus maze), depression (forced swim test), and sexual behavior (lordosis) was investigated using an antisense oligonucleotide (AS-ODN) strategy. If ER is required for anti-anxiety and antidepressant-like effects, and ER is required for sexual receptivity, of E₂, then intracerebroventricular administration of AS-ODNs against these ERs should attenuate these effects and reduce immunoreactivity of ERs in brain regions that mediate these behaviors, such as the hippocampus and ventral medial hypothalamus (VMH). Ovariectomized rats were primed with 17-E₂ (10 g) 48 h before testing (hour 0). At hours 0, 24, and 47.5, rats were infused with saline vehicle, scrambled control AS-ODNs, or AS-ODNs targeted against ER and/or ER, and were tested at hour 48. Rats infused with ER AS-ODNs, alone, or with ER AS-ODNs had significantly decreased open field central entries, decreased plus maze open arm time and entries, increased time spent immobile, and decreased time spent swimming in the forced swim test, and decreased ER immunoreactivity in the brain than did rats administered ER AS-ODNs, vehicle, or scrambled AS-ODNs. Rats that were administered ER AS-ODNs, alone, or with ER AS-ODNs had significantly decreased lordosis and decreased ER immunoreactivity in the brain compared to rats administered ER AS-ODNs, vehicle, or scrambled AS-ODNs. Thus, ER and ER may be required for E₂'s modulation of affective and sexual behavior, respectively.