H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

Serafim, K.R.; Kishi, Marcos Seizo; Canto-de-Souza, Azair; Mattioli, Rosana

doi:10.1590/1414-431x20132770

Cited by 20 publications

(13 citation statements)

References 36 publications

(52 reference statements)

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“…We found a U-shaped dose-response relationship between CLOZ and anxiety. One possible explanation for this comes from the fact that 5-HT 2A (see above) and H 1 receptor blockade has anxiogenic effects in the elevated plus-maze (Serafim et al, 2013 ) while α 1 receptor antagonism is rather anxiolytic in this test (Komaki et al, 2014 ; Skelly and Weiner, 2014 ; Rasmussen et al, 2017 ). The observed net effect on anxiety could thus be a function of the differential contribution of these receptor types depending on CLOZ binding.…”

Section: Discussionmentioning

confidence: 99%

Behavioral Effects of Acute Systemic Low-Dose Clozapine in Wild-Type Rats: Implications for the Use of DREADDs in Behavioral Neuroscience

Ilg

Enkel

Bartsch

et al. 2018

Front. Behav. Neurosci.

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Designer receptors exclusively activated by designer drugs (DREADDs) are popular tools used to manipulate the activity of defined groups of neurons. Recent work has shown that DREADD effects in the brain are most likely not mediated by the proposed ligand clozapine-N-oxide (CNO) but its metabolite clozapine (CLOZ). However, it is not known whether low doses of CLOZ required to activate DREADDs already have DREADD-independent effects on behavior as described for higher CLOZ doses used in previous preclinical studies. To close this gap, we compared effects of acute systemic (i.p.) CLOZ treatment vs. vehicle (VEH) in a wide range of behavioral tests in male wild-type rats. We found that CLOZ doses as low as 0.05–0.1 mg/kg significantly affected locomotion, anxiety and cognitive flexibility but had no effect on working memory or social interaction. These results highlight the need for careful controls in future chemogenetic experiments and show that previous results in studies lacking CNO/CLOZ controls may require critical re-evaluation.

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Section: Discussionmentioning

confidence: 99%

Behavioral Effects of Acute Systemic Low-Dose Clozapine in Wild-Type Rats: Implications for the Use of DREADDs in Behavioral Neuroscience

Ilg

Enkel

Bartsch

et al. 2018

Front. Behav. Neurosci.

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“…[ 16 ] Serafim et al . [ 17 ] reported an important role of H 1 and not H 2 receptors in anxiety-like behavior. H 1 receptor blockers showed increase in brain levels of noradrenaline and 5-HT and no effect on DA.…”

Section: Discussionmentioning

confidence: 99%

Effect of a combination of duloxetine with hydroxyzine on experimental models of anxiety in mice

et al. 2015

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Objective:There is a strong association between depression and anxiety. Duloxetine, an antidepressant agent, is also used in the treatment of anxiety. Hydroxyzine is preferred over benzodiazepines in the treatment of anxiety. Present study was designed to study the impact of a combination of duloxetine with hydroxyzine in treatment of anxiety.Materials and Methods:Mice received intraperitoneal injection of normal saline (10 ml/kg), duloxetine alone (10 mg/kg), hydroxyzine alone (10 mg/kg), and hydroxyzine plus duloxetine (5 mg/kg, each).Results:The in vivo results (elevated plus maze and light/dark transition tests) showed significant anxiolytic activity with the hydroxyzine treatment than the control group. The brain monoamines were significantly increased in hippocampi, cerebral cortices, and whole brain in drug-treated groups than in the control group. The group receiving the combination showed similar results in the in vivo models and in vitro tests (brain monoamine estimations) than respective monotherapies, with the exception of a greater increase of norepinephrine levels in cerebral cortices in duloxetine-treated group.Conclusion:Combination of duloxetine with hydroxyzine is not beneficial in anxiolytic treatment than the respective monotherapies. There is a need to study the pharmacokinetic drug-drug interactions to understand the present study outcomes.

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“…These findings are consistent with Serafim et al (10) who demonstrated the anxiogenic effect of CPA in mice at various doses. It was proposed that the H1 receptor antagonists supress acetylcholine release from the ventral striatum; furthermore, acetylcholine is associated with anxiety-like behaviours in rodents (10).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the anxiolytic and antidepressant effect of CPA was evident in animal models (8,9). However, these results have been challenged by previous findings (10) in which CPA was demonstrated to exert anxiogenic effects in mice.…”

Section: Introductionmentioning

confidence: 92%

Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety

2017

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Abstract. There is a crosstalk between mood disorders and oxidative stress. Chlorpheniramine (CPA), a first generation antihistamine, is hypothesized to have an anxiolytic role at high doses; however, its antidepressant and antioxidant roles have not previously been investigated. The aim of the current study was to evaluate the antidepressant and anxiolytic effects of CPA treatment in association with nitric oxide (NO) and super oxide dismutase (SOD) activity in a mouse model of anxiety. BALB/c mice were divided into unstressed (naïve), control, and CPA-(0.5 mg/kg) and escitalopram-(ESC; 10 mg/kg) treated groups for 3 weeks. Subsequently, they were immobilized for 6 h and subjected to behavioural paradigms as follows: The open field test, the elevated plus maze (EPM) and the forced swim test to investigate motor function, anxiety and depression, respectively. The mice were sacrificed and serum was obtained to detect NO and SOD activity. Compared with the control group, the CPA-treated group demonstrated an antidepressant effect similar to that of the ESC-treated group. In addition, CPA prevented stress-induced NO without affecting SOD activity. CPA did not improve anxiety-like behaviour in the EPM, nor did it improve stress-induced locomotion and rearing, as demonstrated by the OFT. Thus, to the best of our knowledge, this is the first study to evaluate the antidepressant role of CPA in association with NO metabolism. However, further studies are required to elucidate the underlying mechanism.

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H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

Cited by 20 publications

References 36 publications

Behavioral Effects of Acute Systemic Low-Dose Clozapine in Wild-Type Rats: Implications for the Use of DREADDs in Behavioral Neuroscience

Behavioral Effects of Acute Systemic Low-Dose Clozapine in Wild-Type Rats: Implications for the Use of DREADDs in Behavioral Neuroscience

Effect of a combination of duloxetine with hydroxyzine on experimental models of anxiety in mice

Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety

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