0022-534 7 /89 /1413-0656$02.00 /0 THE JOURNAL OF UROLOGY Copyright© 1989 by The Williams & Wilkins Co. Vol. 141, March Printed in U.S.A. THE RAT AS A MODEL FOR THE STUDY OF PENILE ERECTION DAVID M. QUINLAN,* RANDY J. NELSON, ALAN W. PARTIN, JACEK L. MOSTWIN AND PATRICK C. WALSH From the James Buchanan Brady Urological Institute, Johns Hopkins Hospital and the Departments of Urology and Psychology, Johns Hopkins University, Baltimore, Maryland ABSTRACT A model has been developed for the study of penile erection in the Sprague-Dawley rat. Anatomical dissections demonstrate a bilateral ganglion lateral to the prostate called the major pelvic ganglion. This ganglion receives input from the pelvic and hypogastric nerves and innervates the pelvic viscera. A large fiber from the major pelvic ganglion courses along the urethra and innervates the corpus cavernosum, the cavernous nerve. In 40 animals, electrical stimulation of either the cavernous nerve or the pelvic nerve resulted in reproducible repetitive tumescence of the corpora cavernosum. Following ablation of the cavernous nerve, electrical stimulation failed to produce erections. Standard mating behavior tests of mounting, intromission and ejaculation in 38 rats showed that surgical ablation of the cavernous nerve resulted in a decrease in the rate of intromissions and ejaculations compared with sham operated controls. Present models for the study of erection have been limited to the dog, monkey and cat. The rat model presented here offers several advantages over these existing models: 1) the cavernous nerve is easily identified, 2) electrical stimulation is easily accomplished and reproducible, 3) behavioral and neurophysiological studies are possible, and 4) animal purchase, housing, and maintenance costs are low. These advantages make this model a uniquely useful tool in the further study of penile erection. (J. Ural., 141: 656-661, 1989) Present knowledge of penile erection is the result of studies of humans and animals. The animals used in these studies have been the dog, the cat, and the monkey. Purchase and mainte- nance costs of these large animals are considerable and may have hindered research in this field. Also, in recent years diminishing availability of these animals for medical research has become a problem. This led us to search for a less expensive and more readily available animal model for the study of erectile function. The rat may prove to be such an animal model. MATERIALS AND METHODS Anatomy. Fourteen 60 to 100 day old Sprague Dawley rats weighing between 160 and 300 grams underwent dissections to determine the innervation of the pelvic viscera and lower genitourinary tract. The animals were anesthetized with intra- peritoneal pentobarbital (one μg./gm.) and fastened to a padded test-tube rack in the supine position. A midline incision was made from umbilicus to pubis. The penis was denuded of skin and the prepuce circumcised. The testes were retracted, their scrotal attachment was divided and they were packed into the upper abdomen along with loops of bowel. With the aid of a Zeiss dissecting microscope (magnification = XS) the hypogastric nerve, pelvic nerve, major pelvic gan- glion, and the nerve fibers to the lower genitourinary tract were identified. In six animals the anterior pelvis was excised to permit dissection of the urethra, rectum, penis, and pudendal nerve. In two further animals a hindquarter amputation facili- Accepted for publication August 31, 1988. *Requests for reprints: Dept. of Urology, Johns Hopkins Hospital, Baltimore MD 21205. Supported by USPHS grant DH 22201 from the National Institute of Child Health and Development and BRS grant S07RR07041 awarded by the Biomedical Research Support Program, Division of Research Resources. tated the dissection of the nerve roots of the pelvic and puden- dal nerves. Electrical stimulation. In 40 animals electrical stimulation of the cavernous, hypogastric, and pelvic nerves was undertaken using a Grass SD-9 square wave stimulator. Exposure of these nerves, the pelvic viscera, and the penis was accomplished as outlined above. Bipolar silver or platinum wire electrodes were used to stimulate these nerves unilaterally and bilaterally. The exposed end of the electrodes were hooked around the nerve to be stimulated with the positive electrode positioned proximally and the negative electrode two to three mm. distally. Stimulus parameters were one to five volts, frequency of 12 to 24 Hertz, and duration of five milliseconds. In four of these 40 animals the pudendal nerve was also stimulated unilaterally and bilaterally. Exposure of the puden- da! nerves was accomplished by excision of the pubis and superior pubic rami bilaterally. Erections were viewed with a high resolution black and white video camera (Hitachi CCTV camera HV-17TU, Japan) and archived on 1/2 inch video tape with a digital quartz high qualtity video recorder (Panasonic Omnivision PV-4700, Secaucus, NJ) for quantitative image analysis measurements at a later date. Cavernous nerve ablation. Nerve ablation experiments were divided into acute and longterm. In acute nerve ablation exper- iments, the cavernous nerve was divided distal to the point of electrical stimulation in all 40 animals. In five of these animals 1 % lignocaine was topically applied to the nerve distal to the point of electrical stimulation using a fine tipped cotton swab. In longterm experiments 17 animals underwent excision of the cavernous nerve bilaterally. Seventeen other animals served as controls and underwent a sham procedure which exposed (but did not divide) the cavernous nerves bilaterally. All ani- mals were ear tagged for identification. Seven animals from each group were re-explored at one week and 10 animals at one month. At the time of re-exploration the pelvic nerves were stimulated in an effort to produce penile erection. Stimulus parameters were identical to those described above. These 34 rats also took part in the mating behavior tests outlined below. 656