Synergistic antidepressant- and anxiolytic-like effects of harmaline along with cinanserin in acute restraint stress-treated mice

Abstract

Rationale Acute restraint stress (ARS) is an experimental paradigm used for the induction of rodent models of stress-produced neuropsychiatric disorders, such as depression and anxiety. β-carbolines and serotonin (5-HT) systems are involved in the modulation of depression and anxiety behaviors. Objective This study was designed to examine the effects of intracerebroventricular (i.c.v.) injection of cinanserin (5-HT2 receptor antagonist) on harmaline-induced responses on depression- and anxiety-like behaviors in the ARS mice. Methods For i.c.v. infusion, guide cannula was surgically implanted in the left lateral ventricle of mice. The ARS model was conducted via movement restraint at a period of 4 h. Depression- and anxiety-related behaviors were evaluated by forced swim test (FST) and elevated plus maze (EPM), respectively. Results The results displayed that the ARS mice showed depressive- and anxiety-like responses. I.p. administration of different doses of harmaline (0.31, 0.625 and 1.25 mg/kg) or i.c.v. microinjection of cinanserin (1, 2.5, and 5 μg/mouse) blocked depression- and anxiogenic-like behaviors in the ARS mice. Furthermore, co-administration of harmaline (1.25 mg/kg; i.p.) and cinanserin (5 μg/mouse; i.c.v.) prevented the depression- and anxiogenic-like effects in the ARS mice. We found a synergistic antidepressant- and anxiolytic-like effects of harmaline and cinanserin in the ARS mice. Conclusions These results propose an interaction between harmaline and cinanserin to prevent depressive- and anxiogenic-like behaviors in the ARS mice.

Prospecting for a quinoline containing selenium for comorbidities depression and memory impairment induced by restriction stress in mice

“…In this context, we confirmed that ARS caused depressive-like behavior, as demonstrated by increasing immobility time in TST and FST, and memory impairment, as demonstrated by reducing spontaneous alternations in the Y-maze task and reducing exploratory preference for the new object in the ORT. In accordance, other authors showed that the ARS protocol increased the immobility time in TST and FST (Mosaffa et al 2021 ; Niksiyar et al 2021 ). In addition, a study by Wolf ( 2008 ) reported that elevated cortisol responses in humans in the presence of psychosocial stressors triggered impairments in tasks that required participants to remember information previously learned.…”

“…In view of this, ARS was proposed as an accepted stress-inducing experimental model to investigate depressive-like behavior, as well as its relationship with memory impairment in rodents (Baker and Kim 2002 ; Walesiuk et al 2005 ; Li et al 2012 ; Mosaffa et al 2021 ; Niksiyar et al 2021 ). In response to stress, the HPA axis is rapidly activated and results in the release of glucocorticoids (Del Giudice et al 2011 ).…”

Dissection of the relationship between anxiety and stereotyped self-grooming using the Shank3B mutant autistic model, acute stress model and chronic pain model

“…One particularly interesting thing is that anxiety is also common emotional comorbidity in many diseases, such as ASDs, chronic pain, and stress states ( Guo et al, 2018 ; Mosaffa et al, 2021 ; van Steensel et al, 2011 ). It raises a question: what's the relationship between anxiety and stereotyped behaviors.…”

“…To better understand the relationship between excessive self-grooming and anxiety, we selected three mouse models with increasing anxiety-like behavior: Shank3B KO ASDs mouse model ( Peca et al, 2011 ), acute restraint stress mouse model ( Mosaffa et al, 2021 ), and chronic inflammatory pain mouse model induced by complete Freund's adjuvant (CFA) ( Guo et al, 2018 ) to achieve our goals. The aims of the present study were: (a) to compare the self-grooming changes in different anxiety mouse models by analyzing classical grooming parameters and the cephalo-caudal grooming microstructure ( Kalueff et al, 2007 ; Kalueff and Tuohimaa, 2005 ); (b) to understand the roles of anxiety in self-grooming by using an anxiolytic medicine diazepam; (c) to compare the activated brain regions in the progress of self-grooming by using c-Fos labeling strategy.…”

Hallucinogenic drugs and their potential for treating fear‐related disorders: Through the lens of fear extinction

“…Although it is well‐established that MAOIs contained in ayahuasca make DMT bioavailable, it remains unclear how DMT and MAOIs interact to produce various effects of ayahuasca. MAOIs, harmine and harmaline, have both anxiolytic and antidepressant properties (Ahlem et al, 2015; Fortunato et al, 2010; Mosaffa et al, 2021) and can bind to serotonergic 5‐HT 2A receptors with moderate affinity (Ferraz et al, 2019), contributing to ayahuasca's hallucinogenic properties. On the other hand, DMT has high affinity for the 5‐HT 2A receptor, which coupled with the fact that ayahuasca‐induced hallucinogenic state coincided with peak DMT (but not MAOIs) plasma levels, suggests that DMT is the main psychotropic compound of the ayahuasca brew (Brito‐da‐Costa et al, 2020).…”