Toxicity of methylenedioxymethamphetamine (MDMA) in the dog and the rat.

MDMA given orally to dogs and rats for 28 days caused clinical signs like hyperactivity, dilated pupils, and salivation. Medium and high doses led to significantly less weight gain in both species, with initial decreased food consumption that later reversed. In dogs, reduced testicular size and prostatic enlargement occurred at medium and high doses, with testicular atrophy and prostatic hyperplasia seen microscopically. In rats, some clinical pathology values decreased (urinary pH, blood urea nitrogen, glucose, creatinine, LDH, chloride) while others increased (white blood cell count, phosphorus). No brain lesions were found in either species.

Study at a glance

Abstract

Methylenedioxymethamphetamine (MDMA) was administered to dogs and rats orally once a day for a 28-day period to evaluate the morphological and neuropathological effects. Major clinical signs associated with the administration of MDMA in the dog included circling, depression, dilated pupils, hyperactivity, rapid breathing, and salivation. Major clinical signs in the rat included hyperactivity, excitability, piloerection, exophthalmos, and salivation. Gross observations at necropsy in the dog possibly related to administration of the test article included reduced testicular size (one high and one medium dose) and prostatic enlargement in two high-dose animals. No gross lesions were seen in the rats at necropsy. The medium- and the high-dose groups in both sexes in both the rats and the dogs gained significantly less weight than the control and low-dose groups. Food consumption decreased the first week for the high- and medium-dose groups, but a significant reversal toward more normal consumption was noted in the following weeks in both the rats and the dogs. Hematologic, clinical chemistry, and urinalysis values did not appear to be affected by the administration of the test article in the dog. In the rat clinical pathology variables showing a trend to decrease with dose included urinary pH, blood urea nitrogen, glucose, creatinine (females), lactate dehydrogenase (LDH) (females), and chloride. Clinical pathology variables showing a trend to increase with dose included total white blood cell count and phosphorus. Microscopically, testicular atrophy was present in one medium-dose and two high-dose male dogs. Prostatic hyperplasia was present in two high-dose male dogs. No test article-related lesions were seen in the brains of either species.