1. ¹Department of Psychology, The University at Albany – SUNY, Albany, NY, USA
2. ²Department of Life Sciences Research, The University at Albany – SUNY, Albany, NY, USA
3. ³Department of Psychology, University at Hartford, Hartford, CT, USA
4. ⁴Department of Biology, University at Hartford, Hartford, CT, USA
5. ⁵Department of Biological Sciences Research, The University at Albany – SUNY, Albany, NY, USA
6. ⁶The Centers for Neuroscience, The University at Albany – SUNY, Albany, NY, USA

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

Received 6 February 2006; Revised 15 March 2006; Accepted 16 March 2006; Published online 7 June 2006.

Abstract

Intrinsic rewarding effects of estradiol (E₂) may underlie some of the sex differences that emerge postpuberty for the prevalence of drug use and behavioral responses to drugs, but the effects and mechanisms of E₂ for reward have not been well characterized. Conditioned place preference (CPP), as measured by the time spent on the nonpreferred/drug-associated side of the chamber, was utilized as a functional assay to investigate the effects and mechanisms of E₂ in the nucleus accumbens for reward. To determine whether intracellular estrogen receptors (ERs) are important for E₂-induced CPP, rats were administered E₂ (10 g; subcutaneously (s.c.)), which produced CPP in each experiment, and/or ER blockers, such as tamoxifen (Experiment 1), ICI 182,780 (Experiment 2), or antisense oligonucleotides targeted to ERs (Experiment 3). Experiment 1: E₂ significantly increased the time spent on the originally nonpreferred side of the chamber. Coadministration of tamoxifen (10 mg/kg; s.c.) attenuated effects of E₂ to produce a CPP, but tamoxifen alone, increased time spent on the nonpreferred side. Experiment 2: coadministration of ICI 182,780 (10 g/l) to the nucleus accumbens attenuated effects of E₂ to enhance CPP and did not produce a CPP when administered alone. Experiment 3: coadministration of s.c. E₂ with ER antisense oligonucleotides to the nucleus accumbens significantly decreased time spent on the nonpreferred side and expression of ERs in the nucleus accumbens compared to scrambled antisense oligonucleotides or saline vehicle administration. Thus, E₂'s rewarding effects may involve actions at ERs in the nucleus accumbens.