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Toxicity of methylenedioxymethamphetamine (MDMA) in the dog and the rat
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.
Insights
This study investigated the effects of Methylenedioxymethamphetamine (MDMA) in dogs and rats. MDMA caused clinical signs and reduced weight gain, with some dogs showing testicular and prostate changes, but no brain lesions were observed.
Area of Science:
- Veterinary Toxicology
- Pharmacology
- Neuroscience
Background:
- Methylenedioxymethamphetamine (MDMA) is a psychoactive drug with known effects on the central nervous system.
- Understanding the toxicological profile of MDMA in different species is crucial for risk assessment.
Purpose of the Study:
- To evaluate the morphological and neuropathological effects of daily oral administration of MDMA over 28 days in dogs and rats.
- To identify potential target organs and dose-dependent adverse effects.
Main Methods:
- Dogs and rats received daily oral doses of MDMA for 28 days.
- Clinical signs, body weight, food consumption, and clinical pathology parameters were monitored.
- Gross necropsy and microscopic examination of tissues, including the brain, were performed.
Main Results:
- MDMA administration induced significant clinical signs in both species, including hyperactivity and salivation.
- Reduced weight gain and decreased food consumption were observed in medium- and high-dose groups.
- Dogs showed dose-related testicular atrophy and prostatic hyperplasia; rats exhibited some clinical pathology trends but no gross lesions.
- No MDMA-related neuropathological lesions were detected in the brains of either species.
Conclusions:
- MDMA exhibits significant systemic toxicity in dogs and rats, manifesting as behavioral changes and reduced growth.
- Reproductive organs in male dogs appear to be sensitive targets for MDMA toxicity.
- MDMA did not induce observable neuropathological changes in the brains of dogs and rats under the study conditions.