Enkephalin and a potent analog facilitate maze performance after intraperitoneal administration in rats

Met-enkephalin and its analog [D-Ala 2]-Met-enkephalin-NH 2 were administered intraperitoneally (IP) at a dose of 80 μ/kg body weight to hungry rats which were tested over 3 days for their ability to run a complex, 12 choice Warden maze for reward of food. Animals receiving either peptide negotiated the maze significantly ( p < 0.01) faster (74.1 and 73.5 vs. 128.8 sec) and made significantly ( p < 0.01) fewer errors (5.5 and 5.4 vs. 9.1) than animals receiving the diluent vehicle. These findings did not seem to be explained by differences in appetite, thirst, olfaction, or general activity. Rats injected in a preliminary study with an analog, [D-Phe 4]-Met-enkephalin, which has essentially no opiate activity appeared to run the maze as fast as rats injected with [D-Ala 2]-Met-enkephalin-NH 2 and with just as few errors. Injection of morphine seemed to result in slower running times and more errors in the maze. These results demonstrate that enkephalin and some of its analogs can exert significant behavioral changes after IP administration and that these behavioral effects probably can be dissociated from the opiate effects.