Tetrahydroaminoacridine attenuates dizocilpine-induced behavioural changes

The acetylcholinesterase inhibitor tetrahydroaminoacridine (THA) is known to interact with neurotransmitter systems other than the cholinergic, e.g. several studies have shown interaction of THA with the N-methyl-D-aspartate (NMDA) receptor subtype of the glutamatergic system. We therefore investigated whether behavioral changes in rats, caused by the non-competitive NMDA-antagonist dizocilpine, were altered by THA. Spontaneous locomotion was measured in an open field and learning behaviour was evaluated in a spatial learning task in the 8-arm radial maze. Hyperactivity in the open field caused by 0.08 mg/kg i.p. dizocilpine was reversed by 5 mg/kg i.p. THA. Hyperactivity caused by 0.16 mg/kg i.p. dizocilpine was reversed by two THA doses (2.5 mg/kg, 5 mg/kg i.p.). A dizocilpine-induced acquisition deficit in the 8-arm radial maze was attenuated by THA (2.5 mg/kg) on the 6th and 7th day of testing. The effects of THA are discussed with reference to a possible functional glutamate agonism.