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

Abstract

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.

Inhibition of cortical acetylcholine release and cognitive performance by histamine H3 receptor activation in rats

“…Interestingly, bilateral lesions of the tuberomammilary nucleus produce facilitation of learning (Klapdor et al, 1994). In contrast to the hypothesis that histamine impairs cognitive functions, other studies suggest the positive role of the histaminergic system on learning and memory (Kamei et al, 1993), and of RAMH in enhancing spatial learning in a water maze test (Smith et al, 1994). Differences among the behavioural tests explain the discrepancies.…”

Ranitidine analog, JWS-USC-75IX, enhances memory-related task performance in rats

“…Several studies in the past several years (with histamine receptor ligands) have indicated that the endogenous autacoid, histamine, may also play an important role in learning and memory, as well as a number of other functions in the CNS [Smith et al, 1994;Miyazaki et al, 1995]. Therefore, studies to further elucidate the biochemical effects as well as behavioral effects of JWS (and related compounds) are warranted.…”

Interactions between histaminergic and cholinergic systems in learning and memory

“…It should be kept in mind, though, that the systemic administration of these histaminergic compounds can not account for a selective action on restricted brain regions. The scenario is certainly more complex; indeed, R-a-methylhistamine-induced improvement of rat performance in a water maze test [117] calls for a different explanation than simple ACh/histamine interactions. R-a-methylhistamine modulates, in addition to ACh, the release of either 5-HT or noradrenaline [114], and each of these transmitters has been shown to alter performance in a variety of cognitive tests [33].…”

“…Therefore, the impairment of cognition by H 3 receptor agonists is unlikely attributable solely to the modulation of cortical acetylcholine. One might envisage mechanisms other than the cholinergic one, and the finding that R-amethylhistamine improved rodent spatial learning and memory, assessed using a water maze [117], supports this contention. Spatial learning is a primary function of the rodent hippocampus [90], and the water maze test is exquisitely sensitive to hippocampal lesions [87], but H 3 receptor stimulation is expected to decrease hippocampal cholinergic activity [6,7].…”