Long-Acting Deslorelin Implants to Control Aggression in Male Lion-Tailed Macaques (Macaca silenus)
IAAAM 2000
Terry M. Norton1, DVM, DACZM; Linda M. Penfold2, PhD; Bob Lessnau1, MS; Wolfgang Jochle3, DVM, Dr. med. vet., DACT; Sheryl L. Staaden1; Alisha Jolliffe1; Joan E. Bauman4, PhD; Jeff Spratt1, MS
1St. Catherines Island Wildlife Survival Center, Wildlife Conservation Society, Midway, GA, USA; 2White Oak Conservation Center, Yulee, FL, USA; 3Wildlife Pharmaceuticals Inc., Research and Development in Animal Reproduction, Denville, NJ, USA; 4St. Louis Zoo, St. Louis MO, USA

Abstract

All male groupings are problematic for most mammalian species housed in zoological institutions. Aggression between males often necessitates housing them individually without visual contact with each other for long periods of time.1 This can lead to behavioral problems and also takes up valuable holding space. Control of aggression between males is highly desirable since it allows males to be housed together.1

St. Catherines Island Wildlife Survival Center (WSC) maintained a free ranging troop of lion-tailed macaques (LTMs) for 6 yr. During that time several males were born, matured in the troop, and eventually migrated out of the troop. In 1997, it was decided to discontinue the project and the existing troop was sent to another institution. Two surplus males were sent to a second institution, leaving three males at WSC. One male was a retired breeder and the other two were his mature offspring. Aggression through the mesh cage work had been noted between all three males over the years. A variety of traumatic injuries have required veterinary attention.

Deslorelin, an experimental GnRH agonist implant, has shown promise in reducing male aggression and is currently under investigation for this purpose in a number of species (W. Jochle, pers. comm.). The objective of this study was to evaluate the effectiveness and safety of long acting deslorelin implants to control undesirable aggression in intact, mature male lion-tailed macaques. The study is still ongoing at the time of this abstract being written, thus the results are preliminary.

Three mature male LTMs-a 10-yr-old, a 12-yr-old, and a 32-yr-old-were utilized in this study. The animals were initially housed individually with limited visual contact in indoor/outdoor enclosures. They were fed a complete diet of monkey chow, fruit, and vegetables. The animals were handled only under anesthesia. Ketamine (Ketaset, 100 mg/ml, Fort Dodge Laboratories Inc., Fort Dodge, IA) at 5mg/kg and medetomidine (Dormitor, 1 mg/ml, Pfizer Animal Health, New York, NY) at 0.05 mg/kg were utilized throughout the study and the animals were intubated and maintained on isoflurane (Iso Flo, Abbott Laboratories, North Chicago, IL) anesthesia when electroejaculation was performed for semen collection. The health status of each animal was determined prior to the study by a physical examination, complete blood count (CBC), serum biochemistry panel, serum viral antibody panel including herpes B virus, TB testing, fecal examination for parasites and enteric bacterial pathogens, and radiographs. The oldest LTM had only one testicle, severe dental disease, possible calcified seminal vesicles, mild osteoporosis, and degenerative joint disease. Treatment consisted of daily glucosamine HCl and chondroitin sulfate (Nutramax Laboratories Inc, Baltimore, MD), a vitamin D/calcium supplement, and occasional buffered aspirin. The other two LTMs were considered to be healthy. A physical examination, CBC, and serum biochemistry profile were performed during every immobilization. Reproductive evaluations included testicular measurements (i.e., testes length and width, volume, and firmness), subjective prostate size evaluation, semen evaluation (i.e., semen volume, total sperm count, pH, semen concentration, percent motility, and progressive motility) and were conducted prior to implant injection and at 3-mo intervals throughout the study. Fresh feces and serum were collected and frozen at -70°C on a weekly and monthly basis respectively. Behavioral observations were made throughout the study and were most intense when the animals were initially placed together. The behaviors were divided into three categories; aggressive behavior non-contact, aggressive behavior contact, and facial or vocal aggression. A Plexiglas shift door was used prior to placing the animals together so that visual contact aggression behavioral data could be collected.

Serum testosterone levels were considered to be within normal range2 for the three LTM at the beginning of the study. The two younger animals were producing large volumes of normal sperm, while the older male was producing only small numbers of sperm. Each animal received a 6 mg long-acting deslorelin implant by s.c. injection between the shoulder blades on 18 September 1998. The older LTM had negligible serum testosterone levels after the first month and was producing no sperm at 3 mo post-deslorelin injection. This remained unchanged throughout the remainder of the study. The younger two males were still producing normal levels of serum testosterone at the 3-mo evaluation and large volumes of normal sperm were being produced. Fecal testosterone levels were more difficult to interpret and did not seem to correlate well with the serum levels. The 12-yr-old animal's weight had decreased significantly, while the other two LTMs maintained their body weights (Table 1). Another 6 mg of deslorelin was administered s.c. to the two younger males on 18 December 1998.

Over the next 3 mo, serum testosterone levels slowly decreased in both young animals and the 12-yr-old's weight continued to decrease while the 10-yr-old maintained his weight. Semen evaluation at 6 mo (19 March 1999) revealed that both young animals had larger numbers of motile sperm when compared to the two previous evaluations. One week prior to this evaluation, behavioral observations revealed that all three LTMs were much less aggressive towards each other through the plexiglass window. The LTMs were then slowly introduced to each other for short periods of time each day.

Serum testosterone levels and body weights continued to drop over the next 3 mo. All three LTMs were left together for a few hours while being observed. Initially there was a lot of mounting behavior and minor aggression. Grooming behavior became more common over time and less mounting and aggressive behavior were noted. The prostate of all three animals measured ~ 1 cm x 0.5 cm before deslorelin treatment but was barely detectable 3 mo following deslorelin treatment. Also, a coagulem fraction present in ejaculates from the two younger animals collected on 22 September 1998 and 18 December 1998 was absent in subsequent ejaculates. An increase in testes size and morphologically normal spermatozoa on the 18 December 1998 and an increase in total spermatozoa produced on 18 March 1999 for the two younger animals was noted. This is attributable to the short-term increase in circulating testosterone concentrations (Table 1; 18 December 1998) following treatment with a second implant. The 10-mo evaluation revealed significant reduction in motile sperm and numerous spermatocytes in the 10-yr-old's semen and still large numbers of motile sperm in the 12-yr-old's semen. By 20 August 1999, 11 mo into the study, the three animals were together most of the time and showing very little aggressive behavior.

On 19 September 1999, the 32-yr-old was worked up for unusual respiratory sounds and deemed to have megaesophagus and possible aspiration pneumonia based on plain radiograph evaluation. Treatment consisted of clindamycin (150 mg, Greenstone Ltd., Portage, MI) 10 mg/kg b.i.d. and enrofloxacin (Baytril, Bayer Corp, Animal Health, Shawnee Mission, KS) 2.5 mg/kg b.i.d., both drugs were given orally for 14 days. The unusual respiratory sounds improved and regurgitation was never observed. On 22 October 1999, endoscopy was used to confirm the megaesophagus. The LTM died while recovering from anesthesia. Gross necropsy revealed an enlarged esophagus and gas filled gastrointestinal tract, spondylosis, calcified seminal vesicles, cysts in the renal cortex bilaterally, severely worn dentition, and severe degenerative joint disease in a variety of sites. Histopathology revealed a mild plasmolymphocytic esophagitis and enteritis, coagulative necrosis of pancreatic acinar tissue and adjacent fat, renal tubular cysts within the renal cortex, and diffuse atrophy of seminiferous tubules with thickening of the wall with fibrous connective tissue. Although unlikely, it could not be definitely stated that the deslorelin did not play a role in some of these changes. Despite this animal's death, the study was continued with the other two individuals.

During the 14-mo evaluation, the 12-yr-old's semen evaluation revealed significantly reduced numbers of motile sperm, while no sperm was noted on the 10-yr-old's ejaculate (Table 2). Reevaluation 2 mo later revealed similar findings. Results of serum testosterone levels from 21 September 1999 to April 2000 are pending. The two LTMs are currently housed together 24 hrs per day. Reproductive exams, physical exam, and serum testosterone levels are currently being performed every 3 mo.

Preliminary results from this study suggest that deslorelin implants may be useful in creating bachelor groups of LTMs with significant reduction in aggression. Side effects include loss of weight and muscle condition, similar to a castrated animal.

Table 1. Serum testosterone (T) levels (ng/ml) and body weights (wt) of three lion-tailed macaques (Macaca silenus).

Date

32-yr-old
(T/wt)

12-yr-old
(T/wt)

10-yr-old
(T/wt)

22-Sep-98

16.1/9.7

5.6/8.7

7.0/10.5

15-Oct-98

1.0/9.4

6.6/8.6

7.6/10.9

17-Nov-98

1.0/9.4

6.4/8.2

8.0/10.8

18-Dec-98

0.6/9.3

8.6/7.8

8.8/10.5

19-Jan-99

0.7/9.0

5.6/7.5

7.9/9.9

19-Feb-99

0.5/8.9

4.2/7.5

4.6/10.0

19-Mar-99

0.3/8.9

2.4/7.2

0.8/9.7

29-Apr-99

0.3/9.0

2.0/7.4

0.8/9.0

5-Jun-99

0.3/9.6

0.9/7.2

0.7/9.0

13-Jul-99

0.2/9.8

1.3/7.2

0.5/8.8

20-Aug-99

0.2/9.6

1.7/7.1

0.2/8.8

17-Sep-99

NA/9.8

NA/6.9

NA/8.6

22-Oct-99

NA/9.4

NA/7.2

NA/8.8

16-Nov-99

NA

NA/7.1

NA/8.6

21-Jan-00

NA

NA/7.1

NA/8.8

NA=not available

Table 2. Morphometric measurements and sperm traits of three lion-tailed macaques (Macaca silenus) before and after deslorelin treatment (6 mg long-acting implant by s.c. injection on 18 September 1998).

 

Date

Testes
volume
(cm3)

Total
sperm/
ejaculate
(H 106)

Sperm
motility
(%)

Normal
sperm
morphology
(%)

32-yr-olda

22-Sep-98

8.4

0.2

40

-

18-Sep-98

5.7

0

-

-

19-Mar-99

5.8

0

-

-

13-Jul-99

10.3

0

-

-

10-yr-old

22-Sep-98

36

226

56.7

32

18 Dec 1998b

48.3

60.2

30

64

19-Mar-99

30.1

313.8

61.7

35

13-Jul-99

20

0.1

0

2

16-Nov-99

15.6

0

-

-

21-Jan-00

13.7

0

-

-

12-yr-old

22-Sep-98

35.3

20.2

56.7

32

18 Dec 1998b

34.8

9.4

50

68

19-Mar-99

26.2

61.4

55

66

13-Jul-99

17.5

327.5

55

10

16-Nov-99

17

60.4

25

4

21-Jan-00

17.3

55.6

20

12

a No right testis.
b Additional 6 mg deslorelin.

Acknowledgments

Special thanks go to Shelly Angell and Marcie Oliva for their technical expertise and Cheryl Asa for coordinating the endocrinology work.

References

1.  Calle PP, C McClave, JA Basinger, H Walters, BL Raphael, RA Cook. 1998. Use of depot leuprolide and cyproterone to control aggression in an all male California sea otter (Enhydra lutris nereis) colony. Proc. Ann. Mtg. Amer. Assoc. Zoo. Vet., Omaha, Pp. 375-377.

2.  Cranfield MR, NG Berger, B England, SE Kempske. 1992. The search for a reversible male birth control in the lion-tailed macaque as a model for other primate species. Proc. Ann. Mtg. Amer. Assoc. Zoo Vet., Oakland, Pp. 306-319.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Terry M. Norton, DVM, DACZM


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