The gonadotropic and aphrodisiac properties of the alkaloid yohimbine have been the subject of many conflicting reports. These conflicts have not only been due to contradictory results but also to a lack of agreement of which indices would best demonstrate the alleged sex-stimulating properties of this agent. The indices have been as diverse as litter size and number [17], corpora lutea and follicle formation [6, 10, 13, 14, 18], vaginal cytology [5, 6, 10, 11, 14, 15, 18], genital hyperemia [6, 11, 13, 15] and precocious development [6, 10, 14, 18]. Yohimbine has also been implicated as a pituitary stimulant of interstitial cell stimulation hormone (ICSH) secretions [5, 10].

Although yohimbine, like all aphrodisiacs, is alleged to arouse, sustain or increase sexual drive, only a few casual behavioral observations of its effects in animals have been reported [5, 10, 13]. The present study, therefore, investigates the effect of yohimbine HCI on copulatory parameters using controlled and systematic behavioral studies, as well as determining its effect on the pituitary and genitalia of the male rat.

METHOD

Forty-one male Sprague-Dawley rats were arranged into two intact and two prepuberally (21-22 days of age) castrated groups. All animals were caged separately from 25 days of age. Sexual behavior tests were started at 100 days of age. For these tests, each male was placed in a plexiglass observation cage, presented with an estrus female and observed for copulatory performance during 5 weekly 10-min sessions. The frequency, and latency, of mounting, intromission and ejaculation were recorded using the standardized techniques of Beach and Whalen [3].

Starting three days before the first observation session, individuals of one intact and one castrated group began receiving daily subcutaneous injections of yohimbine HCI (K & K Laboratories, Plainview, N.Y.). Twenty mg/kg was administered for 10 days, and 10 mg/kg for the remaining 25 days. The 2 remaining groups served as controls, receiving only the injection vehicle, a 50 % aqueous solution of dimethyl sulfoxide (DMSO).

Each rat was weighed weekly. At the conclusion of the behavioral sessions, all animals were sacrificed and their genitalia examined for hyperemia or other gross abnormalities. The testes, ventral prostate, seminal vesicles and anterior pituitary were then excised, weighed and quick frozen for later study. Haemotoxylin- and eosin-stained sections of the testes were prepared.

Bio-assay of the anterior pituitary glands for ICSH was performed using a variation of the ovarian ascorbic acid depletion method of Parlow [16]. The anterior pituitaries were pooled in groups of two and diluted to 2 mg (wet wt)/ml of normal saline. Three pituitary pools were selected randomly from each of the four groups for bio-assay. Each sample was run in triplicate.

Differences in the number of yohimbine-treated vs control animals which copulated in either the intact or the castrated groups were analyzed by the Fisher exact-probability test. Of those animals which copulated, the Mann-Whitney U test was utilized to determine possible significant differences in the latencies or frequencies of the various copulatory components. Variations in weights or hormone levels were analyzed via the Student’s t test. Pearson product-moment correlation studies were performed between body weight and the various organ weights.

RESULTS

A melting point determination and an ultraviolet spectrophotometric analysis confirmed the structure of the test compound as yohimbine.

The copulatory behavior of the yohimbine-treated animals did not differ from that of their respective controls (Table 1). No significant differences were demonstrated in the percentage of yohimbine-treated vs control animals which copulated during any particular observation session, nor in the latencies or frequencies of the copulatory components.

TABLE 1
Mean Values for Onset of Copulatory Components During the 5 Tests of Sexual Behavior
  Intact Castrated
Behavior
Component
Yohimbine
(8)
Control
(10)
Yohimbine
(12)
Control
(11)
Mount latency (sec)
Intromission latency (sec)
Ejaculation latency (sec)
Mount frequency
Intromission frequency
228.2
321.0
>600
11.7
4.6
188.6
280.9
>600
8.5
8.6
>600


0
>600


0
Number of animals in each group is reported in parentheses.

Lack of ejaculations by intact males during the ten-min test period was unexpected. Beach [1] reported that 9 of 22 male rats, isolated from 21 days of age, ejaculated within fifteen minutes after introduction of a receptive female. After completion of the final ten-min test session, copulatory behavior of those males which had achieved one or more intromissions during this session was observed for an additional five min. Of thirteen males (six yohimbine-treated and seven controls), five animals (including two yohimbine-treated) ejaculated during this extended observation period. Others [7] report that ejaculation usually occurs in the male within ten minutes after introducing a receptive female. Thus, one cannot preclude the possible effect of the vehicle, a 50% aqueous solution of DMSO, as an anaphrodisiac agent.

Home-cage activity, observed for approximately 1 hr every day, indicated no evidence of irritability or hyperexcitability nor were spontaneous erections or other indications of possible hypersexuality observed.

Gross examination of the genitalia at the time of sacrifice failed to reveal hyperemia or other abnormalities in either the yohimbine-treated or the control animals. Weight gain was consistent in all groups. No correlation was seen between body weight and the various organ weights. While a significant increase in the weight of the seminal vesicles was observed in the intact yohimbine-treated males, no other weight differences were apparent (Table 2).

TABLE 2
Average Body and Organ Weights, and ICSH Levels
  Intact Castrated
Organ Yohimbine
(8)
Control
(10)
Yohimbine
(12)
Control
(11)
Whole body
Testes
Seminal vesicles
Ventral prostate
Anterior pituitary
411.93 g
3.53 g
541.71 mga
258.43 mg
9.90 mg
370.24 g
3.59 g
441.62 mg
265.80 mg
9.08 mg
373.55 g

13.65 mg
4.21 mg
14.25 mg
345.97 g

11.36 mg
3.77 mg
13.92 mg
Pituitary ICSH Content
2.12 μg 1.76 μg 9.53 μg 10.02 μg
a p < 0.02
Hormone content expressed as μg/mg (wet wt) of anterior pituitary.

Analysis of the anterior pituitary for ICSH content failed to reveal a statistically significant difference between the yohimbine-treated and the control animals in either the castrated or the intact group (Table 2). As expected, a significant increase in the pituitary ICSH level of the castrated animals was observed.

Histological examination of the testes failed to reveal any significant morphological differences between yohimbine-treated and control animals.

DISCUSSION

Our data indicate that yohimbine HCI administered daily to castrated and intact male rats has no apparent effect on copulatory behavior. The admitted impurity of Engle’s yohimbine solution [8] may explain why he observed hyperexcitability and a heightened sexual aggressiveness in the male mouse.

The absence of hyperemia of the genito-urinary tract, and the failure to demonstrate spontaneous erections in any animal, confirm the previous observations of Sulman and Black [18]. (Admittedly, the vehicle used could explain the absence of hyperemia as DMSO has been reported to have anti-inflammatory properties [4]). Our findings are further in agreement with those of Butcher and Fugo [5] with regard to the ineffectiveness of yohimbine to alter total body weight and weights of the testes, ventral prostate and anterior pituitary. Kit [12] administered 2 mg/kg yohimbine daily for 10 days and reported no difference in the combined weight of the rat’s seminal vesicle and prostate.

Because of the lack of supporting evidence, the increased seminal vesicle weight reported in this study is probably not indicative of an increased level of endogenous testosterone. Failure to remove all of the seminal fluid from the lumen during autopsy could explain this weight variation. All weights were reported on an absolute basis as no correlation was found between the various organ weights and body weight.

In light of these data, the suggestion brought forth by Fugo and Gross [10] that yohimbine may act via the anterior pituitary to release excessive amounts of ICSH is questioned. Not only were ICSH levels consistent in the yohimbine-treated and control animals, but the size of the testes and ventral prostate indicated no differences in endogenous androgen content.

Results with cantharides (“Spanish fly”) administered to male rats have been equally unsuccessful with regard to altering copulatory parameters (Beach, F. Personal communication).

The alleged androgenic and aphrodisiac actions of Pega Palo (Rhynchosia pyramidalis), a woody vine native to the Dominican Republic and Haiti, were also not corroborated under laboratory conditions [9]. These data support the belief that, with the exception of testosterone and related androgens [2], no agent is known which will increase sexual performance in a controlled laboratory environment.

 

REFERENCES

1. Beach, F. A. Comparison of copulatory behavior of male rats raised in isolation, cohabitation and segregation. J. genet. Psycho!. 60: 121-136, 1942.

2. Beach, F. A. and M. Holz-tucker. Effects of different concentrations of androgen upon sexual behavior in castrated male rats. J. comp. physiol. Psychol. 42: 433-453, 1949.

3. Beach. F. A. and R. E. Whalen, Jr. Effects of ejaculation on sexual behavior in the male rat. J. comp. physiol. Psychol. 52: 249-254, 1959.

4. Block, L. H. Dimethyl sulfoxide. Medicinal and pharmaceutical aspects. Drug Cosmet. Ind. 95: 342-346, 462-465, 1964.

5. Butcher, R. L. and N. W. Fugo. Endocrine-stimulating effects of yohimbine hydrochloride. Proc. Soc. exp. Biol. Med. 113: 844-848, 1963.

6. D’Amour, M. C. An attempt to duplicate hormone response by means of drugs. Endocrinology 18: 235-236, 1934.

7. Drori, D. and Y. Folman. The sexual behavior of male rats unmated to 16 months of age. Anim. Behav. 15: 20-24, 1967.

8. Engel, P. Female mating behavior shown by male mice after treatment with different substances. Endocrinology 30: 623, 1943.

9. Farnsworth, N. R., M. Hess, A. F. Fisher, R. F. Martello and L. V. Cammarato. Alleged androgenic and aphrodisiac action of Pega Palo (Rhynchosia pyramidalis). J. Pharmac. Sci. 56: 967-970, 1967.

10. Fugo, N. W. and E. G. Gross. Anterior-pituitary-stimulating action of yohimbine. Endocrinology 31: 529-534, 1942.

11. Hechter, O., M. Lev and S. Soskin. Relation of hyperemia to the action of estrin. Endocrinology 26: 73-79, 1940.

12. Kit, S. M. Effects of ginseng, yohimbine, pantocrine, reserpine and saponin-escin on the prostate and on seminal vesicles in castrated male rats. Farmak. Toks. 25: 629-631, 1962.

13. Kline, M. Est-il possible de provoquer le rut par l’hyperhemie experimentale du tractus genital? C. r. hèbd. Séanc. Soc. Biol. 97: 296-298, 1927.

14. Loewe, S., F. Lange, H. E. Voss and E. Paas. Effect of yohimbine on the vaginal heat phenomena of female rodents. XV. Female sexual hormones. Archsexp. Path. Pharmak. 122: 366-384, 1927.

15.Ludwig, F. and J. Ries. Aphrodisiacs and estrus hormones. Schweiz. med. Wschr. 62: 401-404, 1932.

16. Parlow, A. F. and L. E. Reichert, Jr. Influence of follicle-stimulating hormone on the prostate assay of luteinizing hormone (LH, ICSH). Endocrinology 73: 377-385, 1963.

17. Rumry, F. L. The action of yohimbine on reproductivity. J. Pharmac. exp. Ther. 11: 172-173, 1918.

18. Sulman, F. and R. Black. The alleged endocrine effect of yohimbine. Endocrinology 36: 70-72, 1945.


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