Effects of (R)-alpha-methylhistamine and scopolamine on spatial learning in the rat assessed using a water maze.

The effects of (R)-alpha-methylhistamine ((R)-alpha-MeHA, a selective H3-receptor agonist) and scopolamine (SCOP, a muscarinic antagonist) were investigated on spatial learning and memory in the rat (Hooded Lister) using a water maze (WM). (R)-alpha-MeHA treatment (6.3 and 10 mg/kg IP) had no apparent effect on spatial learning but did result in enhanced spatial recall at the higher dose, assessed by a transfer (probe) test after training. In contrast, SCOP (0.5 mg/kg IP) induced a learning and memory deficit measured both during and after training. In animals treated with (R)-alpha-MeHA and SCOP, (R)-alpha-MeHA partially (6.3 mg/kg) and completely (10 mg/kg) reversed the SCOP-induced deficit during the training phase, while in the post-training transfer test, (R)-alpha-MeHA (10 mg/kg) significantly reduced the SCOP-induced memory deficit. None of the treatments described resulted in impaired visual acuity as demonstrated by a raised platform test. These results are consistent with a role for histamine in cognitive processes and suggest a possible interaction between central histamine and cholinergic mechanisms associated with rodent spatial learning and memory.