Background: Repeated administration of some drugs could result for enhancement of behavioral effects of the drugs. 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 µg/mouse, i.c.v.) decreased the step-down latency on the test day. Repeated pretreatment of histamine (10 and 20 µg/mouse) for three days followed by five days of no drug treatment, prevented amnesia due to post-training histamine (20 µg/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.
