Tetrahydroaminoacridine and D-cycloserine fail to alleviate the water maze spatial navigation defect induced by hippocampal inactivation.

The present study examined the efficacy of single and combined treatment with an anticholinesterase, tetrahydroaminoacridine (i.p.), and a glycine-B site partial agonist, D-cycloserine (i.p.; a positive allosteric modulator of NMDA receptors), in alleviating the deficit in water maze spatial navigation induced by electrolytic lesion of the medial septum or lidocaine infusion into the dorsal hippocampi. In medial septum-lesioned rats, a combination of tetrahydroaminoacridine 3 mg kg(-1) and D-cycloserine 10 mg kg(-1) facilitated acquisition of the water maze test more effectively than either of the drugs alone. Single or combined treatment with tetrahydroaminoacridine 3 mg kg(-1) and D-cycloserine 10 mg kg(-1) had no effect on the water maze deficit induced by hippocampal lidocaine infusion. These results suggest that combined treatment with tetrahydroaminoacridine and D-cycloserine can effectively stimulate water maze spatial navigation, and that functioning of the hippocampus is a prerequisite for this effect.