Opioid-induced linear running in obese (ob/ob) and lean mice

Earlier research has shown that opioids stimulate behavioral activation in mice whereas opioid antagonists attenuate this activation. We conducted an experiment to determine the dose-response curve of FK33824, a potent Met-enkephalin analogue. FK33824 produced an unusual form of behavioral activation we called "linear running" in which the mice ran continuously in one direction and were nearly oblivious to environmental stimuli. This may be the kind of running that occurs naturally during migration. Wheel running activity of genetically obese (ob/ob) and lean (C57BL/6J ?/+) mice was measured following the intracerebroventricular infusion of 0.1, 1.0, 10.0 and 100.0 ng of FK33824. The lowest dose did not alter baseline running, whereas the 1.0 and 10.0 ng doses significantly increased running in both genotypes. We found a genotype difference with the highest dose tested, the lean mice ran at baseline levles and displayed ataxia whereas the obese mice continued to show increased running without ataxia. We hypothesize that genetic differences in the enkephalin mechanisms of C57 lean and obese mice are responsible for linear running.