Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

Abstract

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Hippocampal-Dependent Antidepressant Action of the H3Receptor Antagonist Clobenpropit in a Rat Model of Depression

“…H 3 R activation decreases gamma oscillations ( Andersson et al, 2010 ), which have been correlated positively with cognition ( Jensen et al, 2007 ). Consistent with the effect on gamma oscillations, an extensive battery of studies has revealed that H 3 R antagonists improve attention and memory ( Passani et al, 2004 ; Esbenshade et al, 2008 ; Sander et al, 2008 ), whereas H 1 and H 2 R antagonists inhibit memory formation ( Gianlorenco et al, 2014 ; Taati et al, 2014 ). However, the role of histamine receptors in depression has been less explored and never confirmed in an animal model of depression.…”

Histamine Receptors in the Cross-Talk between Periphery and Brain

“…Blocking either the H 1 and H 2 receptor in the lateral septum decreases anxiety ( Chee and Menard, 2013 ), and both the H 1 and H 2 receptor knockout mice show enhanced emotional learning but reduced spatial learning ( Dai et al, 2007 ). In other experiments, however, only the H 1 receptor antagonist reduces anxiety, whereas the H 2 receptor antagonist has no effect ( Gianlorenco et al, 2014 ). In the hippocampus, a H 2 receptor antagonist, but not a H 1 antagonist, improve learning ( Taati et al, 2014 ).…”

Cerebellar Nonmotor Functions – Approaches and Significance

“…A great body of experimental and clinical data suggests the involvement of the cerebellum in modulation of affects and emotions (reviewed in [87]). It was found that the cerebellar vermis is related to emotional memory consolidation, and a histamine H2 receptor antagonist, ranitidine, applied to the cerebellar vermis impaired this consolidation in mice re-exposed to the elevated plus maze [88].…”