ISSN:
1573-6830
Keywords:
diethylstilbestrol
;
estrogens
;
DAGO
;
opiate receptors
;
binding
;
hippocampal evoked potentials
;
hippocampal slices
;
mouse
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
Notes:
Abstract 1.Several steroids and related compounds can bind to central opiate receptors in whole-brain mouse homogenates. Among these drugs, the synthetic estrogen, diethylstilbestrol (DES), exhibits one of the highest affinities in binding experiments labeling opiate receptors with the nonselective opiate antagonist, [3H]diprenorphine. 2.In the search for a functional correlate to this biochemical finding, we have studied the effects of DES on the mouse hippocampal slice in vitro preparation. 3.Previously, binding studies were performed in hippocampal homogenates, labeling opiate receptors with [3H]diprenorphine or with the μ-selective opiate agonist, [3H]DAGO. DES inhibited [3H]diprenorphine and [3H]DAGO binding, the IC50 values obtained being (1.03 ± 0.16) × 10−5 and (1 ± 0.8) × 10−5 M, respectively. 4.In mice hippocampal slices, we measured the extracellular evoked potentials obtained in the CA1 pyramidal cell layer of the hippocampi and the field excitatory postsynaptic potentials (EPSP) obtained in the stratum radiatum. The presence of DES (10−5 M) induced an increase in the amplitude of the population spikes measured in the pyramidal layer without modifying the field EPSP. This effect is similar to that obtained in the presence of DAGO in this preparation. The effect produced by DES was not modified by the presence of the opiate competitive antagonist, naloxone (10−5 M), or by the opiate alkylating agent, β-chlornaltrexamine(10−5 M). Conversely, in the presence of the transcription inhibitor, actinomycin D (5 μg/ml), the effect produced by DES was inhibited. 5.Our results with DES support the general idea that estrogens increase central excitability. Although diethylstilbestrol can bind to opiate receptors in the hippocampus, the effect induced by this estrogen on hippocampal excitability seems unrelated to a direct action on opiate receptors, and an intracellular effect is suggested.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1006996805017
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