Effect of cyclo-leucyl-glycine in the rat yeast-paw test

Cyclo-leucyl-glycine (CLG) was tested for its ability to produce an antinociceptive effect in the rat yeast-paw test under conditions in which Z-prolyl-(L)leucine (ZPLL) was effective. CLG at doses from 0.1 to 200 mg/kg p.o. given once per day for three days failed to produce an analgesic effect; at 300 mg/kg per day p.o., CLG produced a slight increase in response latencies (less than 1 s). ZPLL (5 mg/kg per day p.o.) tested similarly in the same experiment produced a strong analgesia (greater than 10 s increase in response latencies). Since CLG and ZPLL have both been shown to inhibit opioid tolerance/dependence, whereas only ZPLL has been demonstrated to produce analgesia, it appears as if the mechanisms underlying these two effects are different.