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Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.
HOTCHKISS, M. G., D. S. BEST, R. L. COOPER, AND S. C. LAWS. Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, 34(3):295-302, (2012).
This manuscript was written to report the experimental findings of behavioral and hormone experiments on the effects of administration of a single dose of atrazine to male Wistar rats.
Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To test whether administration of ATR causes hypothalamic-pituitary-adrenal (HPA) axis activation through the production of a generalized stress response resulting from gastrointestinal distress, we conducted both conditioned taste aversion (CTA) and pica behavior experiments. Adult male Wistar rats were given a single oral dose of ATR (0, 5, 25, 50, 100, or 200 mg/kg), the primary ATR metabolite desethyl-desisopropyl atrazine (DACT; 135mg/kg), or lithium chloride (LiCI, i.p.; 127mg/kg; positive control). Results from the CTA experiment demonstrated a clear dose-response for ATR, with a NOEL of 5mg/kg. Interestingly, animals dosed with DACT or LiCI developed aversions comparable to the highest dose of ATR. The DACT results were unexpected given the minimal HPA-axis activation observed following DACT administration and may reflect an alternate learning mechanism in the CTA paradigm. The pica experiment showed that lower doses (5-50mg/kg) of ATR had no effect, as measured 6 and 24 hours post-dosing, nor did DACT. However, the highest dose of ATR (200mg/kg) and LiCI did induce pica behavior at both time points. Overall, results indicate that increases in ACTH and CORT secretion following administration of ATR occur at doses that are without effect on the display of pica behavior, indicating that the HPA-axis activation caused by ATR is not likely the result of gastrointestinal distress.