Rodent meals affect drug tests

July 23, 2012 § Leave a comment

Some lab rodents get to munch all day. Image provided by http://www.flickr.com/photos/jepoirrier/422469526/

Lab rats (the actual ones, not graduate students) and mice are critical for testing drugs for toxicity and other effects before the drugs are given to humans. But what if the cage lifestyle of lab rodents with 24/7 access to rodent kibble is changing the way they react to drugs? In a paper recently published in Chemical Research in Toxicology, nutritionists Gale Carey and Lisa Merrill at the University of New Hampshire explore this question.

Nine months of troubleshooting an experiment got Carey and Merrill thinking about feeding times. They were researching rat fat cell sensitivity to insulin and hit a roadblock, explains Carey. The fat cells lost their insulin sensitivity.  Bewildered, the investigators tried fiddling with every experimental parameter they could think of — new reagents, new glassware, new water, “all the usual suspects,” says Carey. 

One day, “we finally got an experiment to work, but the very next day, with identical conditions and reagents, the insulin response disappeared,” says Carey. The only remaining uncontrolled variable that the researchers could think of was the timing of food intake by their rats.    

Carey was familiar with meal-feeding effects, when animals are given actual meals rather all-day buffets, from research she had done with Saul Brusilow at Johns Hopkins University in the 1980s. So Carey and Merrill decided to conduct a meal-feeding experiment. 

“Sure enough, fat cells from meal-fed rats gave a reproducible and robust insulin response,” she says.  The more the investigators read in the scientific literature about the physiological and metabolic differences between the meal-fed and buffet-fed rodents, “the more convinced we became that research in toxicology and drug metabolism, which is so dependent upon the rodent model, could be dramatically impacted by mode of feeding,” Carey adds.  

Millions of lab rodents are used in drug studies each year.  One suspects most of these animals have continuous access to food. As we all know, the easier it is to get to food, the more we eat.  Lab rodents are no different: They eat more than animals that receive food in the forms of structured meals so they gain more weight and more body fat.  The continuously fed animals also tend to develop abnormally high blood fat levels, high cholesterol, nerve and heart damage, cancer and other disorders.

Carey and Merrill analyzed 54 studies and came to the conclusion that, in rodents, having free access to food is likely to affect the results of tests for the toxicity and cancer-causing effects of new drugs and other substances. The duo suggests that the lack of control over food intake could be the reason why such studies have been varying so much in recent years.

Carey says that although the literature is sparse about the connections between when animals eat and how they react to drugs the studies that do exist are compelling.  “Toxicologists are experts at drug metabolism but aren’t trained to think about nutrition and the impact of food intake on the metabolic and physiologic responses of animals,” she says.  She hopes that the paper sends the message that the timing of  food intake should be considered when designing toxicology experiments.

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