Allopregnanolone increase in striatal N-methyl-D-aspartic acid evoked [3H]dopamine release is estrogen and progesterone dependent

RICARDO J. CABRERA; CLAUDIA BREGONZIO; MYRIAM LACONI; ALEJANDRA MAMPEL

CELLULAR AND MOLECULAR NEUROBIOLOGY.

SPRINGER/PLENUM PUBLISHERS

Lugar: New York; Año: 2002 vol. 22 p. 445 - 454

0272-4340

1. The neurosteroids are compounds derived from steroid hormones and synthesized in the nervous system. They can modulate different neurotransmitter pathways. In previous work we demonstrated that progesterone modulates dopamine release induced by the glutamatergic agonist N-methyl-D-aspartic acid (NMDA).2. The aim of this work was to evaluate a possible modulatory role of the progesteronemetabolite allopregnanolone onNMDA-evoked [3H]dopamine release from corpusstriatum slices obtained from cycling and ovariectomized female rats.3. We used a dynamic superfusion method to evaluate the release of [3H]dopamine.Allopregnanolone at 50–600 nM was added to the superfusion buffer (Krebs–Ringer–bicarbonate–glucose, pH 7.4, with constant O2/CO2 gassing). The results are expressedas a percentage over basal [3H]dopamine loaded by the tissue.4. Allopregnanolone (50 and 100 nM) increased the NMDA-evoked[3H]dopaminerelease from estrus rats. The remaining doses did not show significant changes in the patternof release. This effect was not observed in diestrus rats. The ovariectomy abolished thefacilitatory effect of allopregnanolone on NMDA-evoked 2 [3H]dopamine release.5. Subcutaneous administration of exogenous estrogen (25 mg/rat) and progesterone(1 mg/rat) restored the facilitatory effect on dopaminergic input.6. These results suggest that allopregnanolone is a neurosteroid able to modulatedopamine release in an ovarian-hormone-fluctuation-dependent manner and provide furthersupport for a role of allopregnanolone as a modulator of glutamatergic–dopaminergicinteraction in the corpus striatum.