Background: Repeated administration of certain drugs could result in enhancement of their behavioral effects. In the present study, the effect of repeated administration of histamine on the amnesia induced by post-training administration of the drug was examined. Methods: A single trial step-down inhibitory (passive) avoidance task was used for memory assessment in male NMRI mice. Results: The results showed that post-training administration of different doses of histamine (5, 10 and 20 microg/mouse, i. c. v.) decreased the step-down latency on the test day. Repeated pretreatment of histamine (10 and 20 microg/mouse) for three days followed by five days of no drug treatment, prevented amnesia due to post-training histamine (20 microg/mouse). In contrast, repeated administration of histamine H1 receptor antagonist, pyrilamine (5, 10 and 20 mg/kg) or histamine H2 receptor antagonist, ranitidine (12.5 and 25 mg/kg) 10 min prior to histamine injections, decreased the effect of repeated administration of histamine. Moreover, a similar pattern was seen in animals which received dopamine D1 receptor antagonist, SCH 23390 (0.025, 0.5 and 1 mg/kg) or dopamine D2 receptor antagonist, sulpiride (0.2, 1 and 5 mg/kg) 10 min prior to histamine injections during the repeated pretreatment. Conclusion: The results indicated that both of histamine and dopamine receptor mechanisms may be involved in the effects of repeated pretreatment of histamine on the amnesia induced by the drug.
