Use of Depot Leuprolide Acetate to Control Undesirable Male Associated Behaviors in the California Sea Lion (Zalophus californianus) and California Sea Otter (Enhydra lutris)
Paul P. Calle1; Mark D. Stetter1; Bonnie L.
Raphael1; Robert A. Cook1; Catherine McClave2; JoAnne
Basinger2; Hans Walters2; Kevin Walsh
Abstract
Male marine mammals in zoos and aquariums are sometimes maintained alone or
in same sex groups. This type of housing is desirable for behavioral demonstrations, to prevent
breeding, to control aggressive behavior, or to retain the genetic representation of animals for
future reproduction. These management schemes may be complicated by undesirable male associated
behaviors (aggression, excessive vocalization, anorexia, and loss of operant training).
Castration effectively minimizes or controls unwanted male associated behaviors but anesthesia
and surgery are required and it eliminates the animal's reproductive potential.
In this study, intramuscular administration of leuprolide acetate in a 1
month depot suspension successfully controlled undesirable male associated behaviors in
California sea lions (Zalophus californianus) and California sea otters (Enhydra
lutris) at the Aquarium for Wildlife Conservation. Leuprolide acetate is a long acting, but
reversible, gonadotropin-releasing hormone (GnRH) agonist. Administration initially results in an
increase in follicle stimulating hormone (FSH) and luteinizing hormone (LH) causing elevated
testosterone. A progressive suppression then occurs reducing circulating testosterone levels to
those of a castrate. Leuprolide acetate has been previously demonstrated to suppress testicular
function in Atlantic bottlenose dolphins (Tursiops truncatus).
Three sea lions utilized for behavioral demonstrations developed aggression,
anorexia, excessive vocalizations, and loss of operant conditioning and trained behaviors
associated with seasonal spring and summer rut. Animals ranged from 10 to 23 years old and from
182 to 251 kilograms in weight. Each received 22.5 mg (0.09-0.12 mg/kg) depot leuprolide acetate
at monthly intervals for 6 months (2 April-9 September 1996). Leuprolide was reconstituted with
1.5-9 ml diluent and administered in a pelvic limb by hand injection or projectile dart.
Four sea otters, which had been exhibited as an all male group, developed
intra specific aggression and stress related behaviors (repetitive swimming and diving) as they
matured. Eventually they could no longer be maintained as a compatible group. Otters ranged from
3.5 to 6 years old and from 20 to 33 kilograms in weight at the beginning of the study. Each
otter received 3.75 mg (0.11-0.19 mg/kg) depot leuprolide acetate at monthly intervals.
Initiation of drug administration in each otter was staggered so animals received 3-7 injections
in a 6 month interval. Leuprolide was reconstituted with 0.5-1.5 ml diluent and administered in
the dorsal surface of a pelvic limb by hand injection while the animal was confined in a
restraint device. Marked testicular atrophy occurred in all otters with pre-treatment testicular
length (55.67 ± 5 mm) significantly greater (Paired T test; p<0.05) than post-treatment
length (38.33 ± 5 mm). Testosterone levels were determined at monthly intervals by
radioimmunoassay. The youngest otter had testosterone levels below the assay detection limit
(<O.05 ng/ml) on all sampling dates. Pre-treatment values for the other three ranged from
0.31-2.28 ng/ml. Testosterone levels decreased in these otters at one month post-treatment
(<0.05-0.19 ng/ml) and by two months post-treatment all were undetectable.
One sea lion and 2 sea otters developed moderate to marked anorexia and
depression with injection site lameness, pain, and swelling. Clinical signs were noted 517
days after injection and lasted for up to 3 weeks. Premedication or treatment with
diphenhydramine was ineffective. Pretreatment with flunixin meglumine was not effective, but
administration for 3-7 days after clinical signs developed was helpful in resolving clinical
signs in the sea lion but not the sea otters.
Administration of depot leuprolide acetate was extremely successful in
controlling male associated undesirable behaviors in both the sea lions and sea otters. During
the rut period, the sea lions did not develop anorexia or aggression, did not vocalize
excessively, and were able to be utilized for behavioral demonstrations. It became possible to
maintain the sea otters in a compatible all male group. Advantages of using a GnRH agonist
include no requirement for anesthesia or surgery and reversibility. Disadvantages are the drug
cost, lameness at injection sites and other adverse reactions noted in some animals, and the
necessity for frequent animal handling. Currently, subcutaneous administration and use of a 4
month depot formulation are underway in an attempt to address these limitations. This treatment
has potential application for the control of male associated undesirable behaviors in sea lions
and sea otters in zoos and aquariums if the disadvantages can be overcome.
Acknowledgements
We are grateful to TAP Pharmaceuticals for generous donation of depot
leuprolide acetate, to Karen Drayer and the PKD Trust for financial support, and the veterinary
technicians, animal keepers and trainers for their expert technical assistance.
References
1. Briggs, M.B., W. Van Bonn, R.M. Linnehan, D. Messinger, C.
Messinger, and S.Ridgway.1995. Effects of leuprolide acetate in depot suspension on testosterone
levels testicular size and semen production in male Atlantic bottlenose dolphins (Tursiops
truncatus). Proceedings of the IAAAM, Pp.112-114.