Evidence for the reestablishment of copulatory behavior in castrated male rats with a brain-enhanced estradiol-chemical delivery system.

We have developed a redox-chemical system for brain-enhanced drug delivery of estradiol based on an interconvertible dihydropyridine in equilibrium with pyridinium salt carrier. Estradiol, when combined with the carrier, readily crosses the blood-brain barrier and upon oxidation of the carrier is "locked" in the brain. The aim of this study was to evaluate the effects of an estradiol-chemical delivery system (E2-CDS) versus an equimolar dose of estradiol-17-valerate (E2-VAL) on copulatory behavior in orchidectomized rats. The data revealed that a single dose of E2-CDS was more efficacious than E2-VAL in stimulating mounting behavior (percent responding) and the effect was 100% through 5 weeks. E2-CDS increased intromission behavior more than E2-VAL through 28 days. Mount and intromission latencies were reduced by E2-CDS to a greater extent and for a longer time (28 days) than E2-VAL. Neither form of estradiol restored ejaculation parameters or penile reflexes. These data suggest that E2-CDS causes a potent and long-acting stimulation of proceptive and consummatory components of male sexual behavior, presumably acting through the local brain-release of estradiol.