Slowing the Rat Race.

Low-Dose Dioxin Alters Behavior

Concentrations of a common toxicant too low to cause reproductive abnormalities can still alter behavior in rats, according to a team of researchers led by Vincent Markowski of the University of Southern Maine in Portland [EHP 109:621-627]. The team studied the effects on female rats of perinatal exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD. The study is one of very few to focus on TCDD's behavioral effects, says principal investigator Bernard Weiss of the University of Rochester School of Medicine and Dentistry in New York. Many studies over the past decade have centered instead on TCDD's capacity to interfere with the development of sexual organs and reproductive fitness.

Humans are exposed to the ubiquitous chemical mostly by eating meat, dairy, fish, and poultry products. TCDD is produced from the combustion of plastics and through some manufacturing processes, including paper bleaching. Air currents and water deposition scatter the contaminant, which settles on crops and waterways, where it begins its climb up the food chain. TCDD concentrates in fat and has a half-life in humans of 7-10 years.

The team limited their study to female rats because each sex is affected differently by TCDD, and many rat behaviors are sex-specific. One of those uniquely female behaviors is increased use of a running wheel during estrus, when the female is fertile and sexually receptive. To measure motivation, the researchers developed a running wheel with a brake. The rats were trained to press a lever a certain number of times to release the brake so they could run. The wheel could be rotated for a set time, then would stop. Each time the rats wanted to resume running, they had to release the brake.

Female rats were exposed to TCDD through a single dose given to their mothers by gavage on the eighteenth day of gestation, when the fetal brain is developing a variety of different neural mechanisms. The mother rats received TCDD doses of 20, 60, or 180 nanograms per kilogram body weight (ng/kg). The lowest of these doses is comparable to the typical human body burden. The researchers then conducted the motivation portion of the experiment with the adult offspring.

The researchers found a direct correlation between the rats' exposure to TCDD and their motivation to run on the wheel: the more TCDD the rat was exposed to, the fewer running opportunities she earned. When the wheel was set to turn only after the rat pressed the release lever 20 times, for example, the control group ran an average of 8.3 times per hour. The group exposed to the lowest TCDD dose ran an average of 6.5 times per hour. The group exposed to the highest dose ran an average of 2.7 times per hour.

Whether TCDD causes analogous effects in humans is unknown, although the researchers point out that the average body burden in humans--estimated in 1995 by the U.S. Environmental Protection Agency at 13 ng/kg--was high enough to alter rats' behavior; the researchers extrapolated that a 10% change in the rats' behavior was noted at maternal TCDD exposures of 7-8 ng/kg.

The researchers believe that TCDD's damper on rat motivation extends beyond the running wheel. While other researchers have studied the anatomic and physiologic abnormalities that interfere with reproduction in exposed animals, Markowski and colleagues suggest that TCDD in the fetal brain also alters sexual motivation as well as copulatory behavior itself. They cite earlier research revealing that male rats exposed prenatally to TCDD take longer to begin copulating when allowed access to receptive females--perhaps, the researchers speculate, because of TCDD's motivational effects.