[Abstract Title]. - Society for Neuroscience

Poster
279. Steroids and Plasticity I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 279.16/MM30
Topic: E.01.c. Steroids and plasticity
Support: NINDS NS48141
T32 HD007048
Title: Investigation into the mechanisms mediating the rapid effect of 17ß-estradiol in the
striatum
Authors: *H. YANG 1 , E. M. PECKHAM 2 , J. B. BECKER 1 ;
1 MBNI, 2 Psychology, Univ. Michigan, Ann Arbor, MI
Abstract: 17ß-Estradiol (E2) acts rapidly and directly on the striatum to enhance amphetamine
(AMPH) stimulated dopamine (DA) release. In these experiments, we investigated the
mechanisms mediating the action of estradiol in the striatum. We have shown in previous studies
that estradiol also rapidly inhibits L-type calcium channels in medium spiny neurons from
striatum. Since medium spiny neurons are GABAergic, we hypothesized that estradiol inhibits
the release of GABA, resulting in reduced GABA activity at GABA-B receptors and enhanced
stimulated DA release through a release of inhibition. In one series of experiments we
investigated whether the effect of estradiol on AMPH-induced DA in dialysate can be blocked by
the GABA-B agonist baclofen. Female rats were ovariectomized (OVX) and 2 weeks later
received bilateral guide cannula implants aimed at the striatum. Estradiol was administered s.c.
(5 µg estradiol benzoate, EB) or intrastriatal via the probe (5 ng E2/ml). Intrastriatal E2 or
systemic EB enhanced the AMPH-induced (2.5 mg/kg) increase in DA. This increase was
blocked by systemic baclofen (5 mg/kg), but not intrastriatal baclofen (300 µM) delivered via the
probe. Since we did not see an effect of intrastriatal baclofen, we went on to investigate other
possible mechanisms mediating the effect of estradiol in the striatum. Experiments from the
Mermelstein laboratory have indicated that the effect of estradiol in the striatum is mediated by
the coupling of the estradiol receptor ERα to MGluR5 receptors. So, we investigated the effect of
blocking mGluR5 with 2-methyl-6-(phenylethynyl) pyridine (MPEP, 10 mg/kg) on intrastriatal-
E2 enhancement of AMPH-induced DA in dialysate. Preliminary results indicate that MPEP
prevents the effect of intrastiatal E2 to enhance AMPH-induced DA in dialysate.
Disclosures: H. Yang , None; E.M. Peckham, None; J.B. Becker, None.