Neurobiologyof Aging, Vol. 13, pp. 175-177. ¢ Pergamon Press plc, 1991. Printed in the U.S.A.

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BRIEF COMMUNICATION

Age-Related Changes in Apomorphine-Induced Erections S. V A R R I N A N D J. P. W. H E A T O N t

Human Sexuality Group, Department of Urology, Queen's University, Kingston, Ontario K7L 2V7 R e c e i v e d 20 A u g u s t 1990; A c c e p t e d 25 J u n e 1991 VARRIN, S. AND J. P. W. HEATON. Age-related changes in apomorphine-induced erections. NEUROBIOL AGING 13(1) 175-177, 1992.--Advancing age produces a noticeable and well-documented decline in erectile function in humans. The effects of aging on the ability of apomorphine to stimulate erection and yawning behavior in rats was studied in our bioassay for potency. At the age of seven months, rats failed to respond to the same dose of apomorphine which, just one month earlier, produced erections. Erectile function was then tested in thirty-two seven-month-old rats naive to apomorphine injections, and these rats also failed to respond. Experimentally naive rats of six months of age were then tested and apomorphine produced reliable erections. It is felt that an alteration in dopamine autoreceptor function may be occurring in the central nervous system of rats at approximately seven months of age rendering them incapable of responding to apomorphine with penile erections. Aging

Erections

Apomorphine

Impotence

SEXUAL dysfunction is a common problem in aging males (12). Impotence, which can be defined as the inability to develop an erection sufficient for successful coitus, is always an abnormal state and should not be considered the inevitable companion of aging. A landmark study by Kinsey (9) found that up to age 40, 2% of men had become permanently impotent, that rate jumped to 6.7% at age 55 and 18.4% by age 60. By age 80, Kinsey found that 75% of men had become impotent. While only about 15% of men over age 80 report engaging in sexual intercourse (13), over 50% of males report continued interest in a sexual relationship (22). It has been estimated that one in three males over the age of forty will consult his physician regarding difficulty in obtaining erections sufficient for intercourse (18). In the face of an everincreasing average age in the population, we consider the problem of erectile failure in the aged important and one that demands immediate attention. The lack of an adequate and easily accessible animal model for penile erection has hampered research efforts in the past (1). An examination of the pathophysiological changes occurring during erectile function and dysfunction in animals may improve the understanding of the pathophysiology of impotence in humans. Recently we have described a reliable animal model for potency in rats (5), and thus the effects of factors known to be associated with high impotence rates can now be examined in an animal model.

The administration of low doses of apomorphine (APO) possesses the ability to produce erections in rats (3, 6, 7); this phenomenon is now being harnessed and established as an animal bioassay for potency. APO is thought to produce erections by its action on the dopamine receptor, more explicitly, the presynaptic or D2 dopamine receptor (23), although recent evidence has questioned this mechanism (19). In a pilot experiment using normal rats injected with APO noticeable changes were found in the erectile response as a function of aging. These changes in potency status were noted to occur between six to seven months of age. The present study was undertaken to determine whether age-related changes would alter the erectile response to APO administration. METHOD Male Wistar rats (430-500 g at five months of age) were obtained from Charles River Laboratories (St. Constant, Quebec). Animals were housed in individual stainless steel wire cages. Lighting conditions were maintained on a twelve-hour light/dark cycle with the dark cycle commencing at 1850 hours. Ambient room temperature was maintained at 24°C and relative humidity at approximately 50%. The experiment was conducted in 3 phases. In each phase rats were given a four-week period to acclimatize to their new environment. At the end of the four-week period, the rats were weighed, divided into equal groups of 8 animals per group for

tRequests for reprints should be addressed to Dr. Jeremy P. W. Heaton, Department of Urology, Queen's University, Kingston, Ontario K7L 2V7 Canada.

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dures identical to those of the previous phases were lhen carried out. RESU[,FS

0

20

40

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120

APOMORPHINE DOSE (~tfl/kg)

FIG. 1. This figure shows a decreased number of erections ( _+standard error) at nearly all doses of apomorphine as a function of aging.

phases 1 and 2, 6 animals/group for phase 3, and behavioral observations were initiated. Rats were transported from the housing facility to the experimental room, after which time the study animal was placed in the test cage (26x 18x 18 cm). The room light was dimmed, except for sufficient light suitable for videomonitoring, and a wire grid was placed on top of the test cage as a cover. Each rat was given a 10-minute habituation period to the test cage, at the beginning of each trial. At the end of the ten-minute habituation period, a pseudo-randomly chosen preassigned dose of apomorphine or vehicle [ascorbic acid (0.5 mg/kg) dissolved in normal saline] was administered to the rat (5 ml/kg). APO and vehicle were prepared fresh daily and were given subcutaneously (SC) in the loose skin of the back of the neck. Animal behavior was then observed by means of a Hitachi video camera (VK-C 1500, Hitachi Ltd. Tokyo, Japan) connected to a Hitachi monitor (MT-2860, Hitachi Ltd., Tokyo, Japan) in an adjacent room. The video camera was placed underneath and to the side of the test cage to obtain the best view of the penile response (see Fig. 1). Each animal was given a thirty-minute observation period in which time the number of erections were counted and tabulated by the experimenter. An erection was counted when pelvic thrusts were followed by an upright stance, the emergence of the glans penis and distal penile shaft. Yawns were also counted. At the end of the thirty-minute observation period the animal was returned to the home cage and another animal was tested. In phase 1 of the experiment, animals were assigned to 5 groups, vehicle or 20, 40, 80 and 120 p.g/kg of APO. The rats were tested at six months of age and were not tested again for thirty days. At the completion of the thirty-day rest period, animals were retested (now seven months old) with the identical procedures and dosages of the previous experimental session. The second phase of the experiment consisted of the testing of thirty-two rats naive to APO injections but age matched (seven months) to the previously tested rats. The older rats were randomly divided into four groups and each group was assigned a dose of APO. The vehicle group was eliminated in this phase of the experiment. Experimentation was conducted in an identical fashion to the previous two sessions in the first phase of the experiment. In the third phase of the experiment 6 experimentally naive rats that were the same age as the rats at the beginning of "phase 1" of the experiment (six months) were tested. Animals were weighed and an APO dose of 80 txg/kg was chosen as a representative dose and administered to each rat. Experimental proce-

Results of phase 1 of the experiment were analyzed using a within group one-way analysis of variance (ANOVA) to determine changes in erectile behavior in response to various doses of APO between six- and seven-month rats. Results reveal that over the four APO doses administered, rats at six months of age responded with significantly more erections than when tested at seven months of age, F(1,7)= 15.45 p

Age-related changes in apomorphine-induced erections.

Advancing age produces a noticeable and well-documented decline in erectile function in humans. The effects of aging on the ability of apomorphine to ...
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