Nicotine and D-cycloserine enhance acquisition of water maze spatial navigation in aged rats

WE investigated the effect of nicotine, a nicotinic agonist, and D-cycloserine (DCS, a partial glycine-B agonist of the N-methyl-D-aspartate (NMDA) receptor complex) on aging-induced defects of water maze (WM) spatial navigation in rats. Nicotine (0.3 mg kg, s.c.) or DCS (10 mg kg, i.p.) enhanced acquisition of the WM task. A combination of subthreshold doses of nicotine (0.1 mg kg) and DCS (3 mg kg) improved WM acquisition. A subthreshold dose of a competitive NMDA antagonist, CPP (1 mg kg), blocked the effect of nicotine (0.3 mg kg) on WM acquisition. A nicotine antagonist, mecamylamine (10 mg kg), impaired WM acquisition and had no effect on retention, but did not block the effect of DCS 10 mg kg. The results suggest that nicotine and DCS synergistically enhance spatial navigation in aged rats.