The role of histamine on learning and memory

Abstract

It is well known that the central cholinergic system is intimately related to the modulation of learning (acquisition) and memory processes (retention and retrieval) in humans and animals (Haroutunian et al., 1985). Actually, there are many reports about the ameliorating effects of cholinergic drugs on memory impairment induced by transient cerebral ischemia (Yamamoto et al., 1987), electroshock (Sakurai et al., 1989) or anticholinergic drug administration (Yamamoto and Shimizu., 1987). On the other hand, it has been reported that classic H1 antagonists such as diphenhydramine, pyrilamine and promethazine provided potent depressant actions on the central nervous system (CNS) in many different situations including learning and memory (Winter and Flataker, 1951). Kamei et al. (1981a) demonstrated that diphenhydramine and promethazine induced not only a drowsy pattern in EEGs characterized by high voltage and slow waves but also an inhibition of the EEG arousal response induced by electrical stimulation of the midbrain reticular formation. Tasaka et al. (1985) reported that diphenhydramine, pyrilamine and promethazine caused a potent suppression of the two-way conditioned avoidance response (retardation of memory retrieval) in rats. In connection with this, de Almeida and Izquierdo (1988) found that immediate posttraining after intracerebroventricular (i.c.v.) administration of histamine at doses of 1 and 10 ng facilitated retention performance of step-down inhibitory avoidance behavior (passive avoidance response) measured 24hr after drug administration in rats. In addition, this histamine-induced effect was inhibited by the simultaneous administration of promethazine (1000 ng) and cimetidine (1000 ng), indicating that histamine-induced facilitation of memory retention is mediated via both H1 and H2 receptors. Bhattacharya (1990) also reported that histamine at doses of 1, 5 and 10 μ g produced a dose related dual effect on learning acquisition and retention of memory, with the lower two doses facilitating and high dose retarding the memory paradigms. In these two studies, however, normal animals were used for estimating the drug effect. This chapter provides information about the role of histamine on learning and memory not only in normal but also in some amnesic animals.