Figure 3. Schematic presentation of the dual action of estrogens hypothesis.

The figure illustrates the overlapping dichotomies between the cellular mechanisms mediating estrogens action (A-B), the separate controls of sexual motivation and sexual performance (C-D) in male quail, and the appetitive and consummatory phases of drug addition in rats and mice (E-F). A. Estrogens such as estradiol-17β (E₂) signal at the membrane level by binding to estrogen receptors located at this level only (GPR30, Gq-mER) or to a receptor that is found both in the nucleus and at the membrane (ERα, ERβ) but is associated at the membrane with a metabotropic glutamate receptor (mGluR). This modifies the activity of intracellular signaling cascades that affect behavior either directly or via indirect genomic effects. B. Alternatively, steroids including E₂ bind to intracellular receptors that will then act as ligand-activated transcription factors to modulate production of new mRNA and new proteins that will affect behavior. C. E₂ rapidly modulates appetitive sexual behavior in male quail such as the rhythmic contractions of the cloacal gland or the learned social proximity response illustrated here (male looking at a female through a narrow “window”) by acting at the neuronal membrane level. D. A more prolonged action of E₂ presumably at the nuclear level is needed to activate copulatory behavior sensu stricto illustrated here by the cloacal contact of a male with a female. E. The appetitive responses displayed by rodents to have access to a drug, such as lever pressing on a progressive ratio of operant conditioning, are increased within 30 minutes by an E₂ treatment acting presumably via an ER associated at the membrane level with a mGluR. F. In contrast, consummatory self-administration of drug by intracerebral injections as observed in a FR1 schedule of operant conditioning (each lever pressing results in drug delivery) seems to be affected after only several days of exposure to E₂, suggesting a genomic control by the steroid. See text for additional explanations.