Low-dose thioperamide injected into the cerebellar vermis of mice immediately after exposure to the elevated plus-maze impairs their avoidance behavior on re-exposure to the apparatus

Abstract

The present study investigated the effect of thioperamide (THIO), an H3 histaminergic receptor antagonist, microinjected into the cerebellar vermis on emotional memory consolidation in male Swiss albino mice re-exposed to the elevated plus-maze (EPM). We implanted a guide cannula into the cerebellar vermis using stereotactic surgery. On the third day after surgery, we performed behavioral tests for two consecutive days. On the first day (exposure), the mice (n=10/group) were exposed to the EPM and received THIO (0.06, 0.3, or 1.5 ng/0.1 µL) immediately after the end of the session. Twenty-four hours later, the mice were re-exposed to the EPM under the same experimental conditions, but without drug injection. A reduction in the exploration of the open arms upon re-exposure to the EPM (percentage of number of entries and time spent in open arms) compared with the initial exposure was used as an indicator of learning and memory. One-way analysis of variance (ANOVA) followed by the Duncan post hoc test was used to analyze the data. Upon re-exposure, exploratory activity in the open arms was reduced in the control group, and with the two highest THIO doses: 0.3 and 1.5 ng/0.1 µL. No reduction was seen with the lowest THIO dose (0.06 ng/0.1 µL), indicating inhibition of the consolidation of emotional memory. None of the doses interfered with the animals' locomotor activity. We conclude that THIO at the lowest dose (0.06 ng/0.1 µL) microinjected into the cerebellum impaired emotional memory consolidation in mice.

Systemic injection of an H4 receptor agonist induces a decrease in CREB and pCREB levels in the cerebellar vermis and prefrontal cortex in mice

“…In addition to the high affinity demonstrated by the drug to the H4 receptors, VUF-8430 also has an affinity to the H3 receptors as an agonist (5). We believe that the effect was, at least in part, due to the H4 receptors based on the comparison of different results obtained from previous studies involving the H3 receptors (19,20) and our previous study (7). However, there is a need for further studies to investigate the role of the H4 histaminergic receptors in the CNS, since this study was the first to investigate the action of this agonist via western blot analysis of protein expression in structures linked to memory.…”

The cerebellum and anxiety

“…Various histaminergic receptors in the cerebellar vermis have been implicated in emotional memory (Gianlorenco et al, 2011(Gianlorenco et al, , 2012Costa et al, 2013;Fernandes et al, 2017). This series of experiments established the role of the histaminergic system in lobules IV/V on anxiety-related emotional memory consolidation via the actions of histaminergic receptors H1, H3 and H4.…”