Emotional memory consolidation impairment induced by histamine is mediated by H₁ but not H₂ receptors

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• 作者：A.C.L. Gianlorenç ; o^a ; K.R. Serafim^a ; A. Canto-de-Souza^b ; R. Mattioli^a ; ^{mattioli@ufscar.br}
• 关键词：EPM ; elevated plus maze ; SAL ; saline ; HA ; histamine ; CPA ; chlorpheniramine ; RA ; ranitidine ; % OAE ; percentage of open arms entries ; % OAT ; percentage of open arm time ; CNS ; central nervous system ; OAE ; open arm entries ; EAE ; enclosed arm entries ; OAT ; time
• 刊名：Brain Research Bulletin
• 出版年：2012
• 出版时间：1 December, 2012
• 年：2012
• 卷：89
• 期：5-6
• 页码：197-202
• 全文大小：480 K

文摘

Histaminergic fibers are present in the molecular and granular layers of the cerebellum and have high density in the vermis and flocculus. Evidence indicates that the cerebellar vermis is involved in memory consolidation. Recently, we demonstrated that when histamine is microinjected into the cerebellar vermis it results in impaired emotional memory consolidation in mice that are submitted to the elevated plus maze (EPM). This study investigated whether histamine impairment was mediated by the H₁ or H₂ receptors. The cerebellar vermis of male mice (Swiss Albino) were implanted using a guide cannula. Three days after recovery, behavioral tests were performed in the EPM on two consecutive days (Trial 1 and Trial 2). Immediately after exposure to the EPM (Trial 1), animals received a microinjection of histaminergic drugs. In Experiment 1, saline (SAL) or histamine (HA, 4.07 nmol/0.1 ¦Ìl) was microinjected 5 min after pretreatment with the H₁ antagonist chlorpheniramine (CPA, 0.16 nmol/0.1 ¦Ìl) or SAL. In Experiment 2, SAL or HA was microinjected into the mice 5 min after pretreatment with the H₂ antagonist ranitidine (RA, 2.85 nmol/0.1 ¦Ìl) or SAL. Twenty-four hours later, the mice were re-exposed to the EPM (Trial 2) under the same experimental conditions but did not receive an injection. On both days, the test sessions were recorded to enable analysis of the behavioral measures. The decrease in open arm exploration ( % entries and % time spent in the open arms) in Trial 2 relative to Trial 1 was used as a measure of learning and memory. The data were analyzed using the two-way analysis of variance (ANOVA) and Duncan's tests. In Experiment 1, the Duncan's test indicated that the mice entered the open arms less often ( % OAE) and spent less time in the open arms ( % OAT) in Trial 2 after being microinjected with SAL + SAL, SAL + CPA and CPA + HA. However, the animals that received SAL + HA did not enter the open arms less frequently or spend less time in them, which was significantly different from the CPA + HA group. The results of Experiment 2 demonstrated that the % OAE and % OAT in Trial 2 were different from Trial 1 for the groups that were microinjected with SAL + SAL and SAL + RA. The animals that were microinjected with RA + HA or with SAL + HA did not show a reduction in % OAE. These results demonstrate that the animals treated with HA did not avoid the open arms less on retesting and indicated that CPA did not alter the behavior parameters but did revert the histamine-induced impairment of memory consolidation. Furthermore, the H₂ antagonist RA, at the dose used in this study, did not affect memory consolidation and failed to revert histamine-induced impairment.