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

The present study examined the efficacy of single and combined treatment wi th an anticholinesterase, tetrahydroaminoacridine (i.p.), and a glycine-B s ire partial agonist, D-cycloserine (i.p.; a positive allosteric modulator o f NMDA receptors), in alleviating the deficit in water maze spatial navigat ion induced by electrolytic lesion of the medial septum or lidocaine infusi on into the dorsal hippocampi. In medial septum-lesioned rats, a combinatio n of tetrahydroaminoacridine 3 mg kg(-1) and D-cycloserine 10 mg kg(-1) fac ilitated 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 t hat combined treatment with tetrahydroaminoacridine and D-cycloserine can e ffectively stimulate water maze spatial navigation, and that functioning of the hippocampus is a prerequisite for this effect. (C) 1999 Elsevier Scien ce B.V. All rights reserved.