Minaprine facilitates acquisition and retrieval of an active avoidance response in the rat

The nootropic activity of 3-(2-morpholino-ethylamino)-4-methyl-6-phenyl-pyridazine dihydrochloride (minaprine) has been investigated in intact male, adult Long Evans rats by means of an active avoidance paradigm. In the light-dark box apparatus, the rat had to learn the active avoidance response of going out of the normally preferred dark chamber to avoid electric foot-shocks. These were administered during one trial per day for 3 consecutive days (acquisition period). After a 72-h interval, rats underwent, for 3 consecutive days, one trial per day in which punishments were omitted (retrieval period). In the first experiment, rats were injected IP with minaprine (5, 10, and 25 mg/kg b.w.) 30 min before each trial of both periods. Rats injected with the two lower dosages showed better responding during the retrieval period than controls (saline). On the contrary, the highest dosage impaired active avoidance during both periods. In Experiment 2, minaprine (10 mg/kg b.w.) was administered either only during the acquisition or only during the retrieval period. In both instances, active avoidance was equally enhanced, if compared to controls (saline), only during the retrieval period. The results are discussed on the basis of the known facilitating activity on cholinergic systems of this compound. It is concluded that minaprine acts positively both on acquisition and retrieval of mnemonic traces.