Effects of ketamine, a noncompetitive NMDA antagonist, on the acquisition of the lever-press response in rats.

We analyzed the effects of ketamine, a noncompetitive NMDA antagonist, on the acquisition of the lever-press response in the Skinner box and on motor performance both in the open field and in the inclined screen. Ninety-six adult male Wistar rats were assigned at random to eight different groups (n = 12). The first four groups received an acute intraperitoneal (IP) injection of: (a) physiological saline, (b) 4 mg/kg ketamine, (c) 8 mg/kg ketamine, or (d) 12 mg/kg ketamine, and the subjects were tested in a free lever-press response shaping in the Skinner box. The second four groups received the same substances and doses as the first four, but the subjects were tested for locomotor activity in an open field and tested immediately afterwards for motor performance in an 80 degrees inclined screen. Results showed that ketamine impaired the acquisition of the lever-press response in a dose-dependent manner, with no effects on ambulation in the open field nor on length of stay in the inclined screen. These results suggest that ketamine effects on the acquisition of the lever-press response cannot be attributed to a motor impairment, indicating a possible specific effect of ketamine on the associative learning acquisition.