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Synergistic Anxiolytic-Like Effect of Cppg and Harmaline in Non-Stressed and Acute Restraint Stress (Ars) Mice Publisher Pubmed



Hasankareem N1 ; Alijanpour S2 ; Zarrindast MR3 ; Khakpai F4
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  2. 2. Department of Biology, Faculty of Science, Gonbad Kavous University, Gonbad Kavous, Iran
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

Source: Neuroscience Letters Published:2025


Abstract

Many studies revealed the role of metabotropic glutamate receptors (mGluRs) and harmaline in the modulation of anxiety-related behaviors. This study aimed to determine a possible interaction between harmaline and group III mGluR on the modulation of anxiety-correlated behaviors. The left lateral ventricle of male mice was unilaterally cannulated. Acute restraint stress (ARS) was induced by movement restraint for 4 h. Anxiety-like behaviors were measured using an elevated plus maze. The results showed that induction of ARS during 4 h reduced the percentage of time spent in open arms (%OAT) and percentage of entries to open arms (%OAE) without changing locomotor activity, indicating anxiogenic-like responses. Intraperitoneal (i.p.) administration of harmaline (2 mg/kg) increased %OAT in non-stressed and ARS mice, presenting anxiolytic-like responses. Intracerebroventricular (i.c.v.) infusion of CPPG (potent group III mGlu antagonist, 70 µg/mouse) induced anxiolytic-like behavior due to the augmentation of %OAT in non-stressed and ARS mice. Co-treatment of CPPG (70 µg/mouse, i.c.v.) along with harmaline (1 mg/kg, i.p) induced an anxiolytic-like effect. I.c.v. infusion of L-AP4 (selective group III mGlu agonist) or co-administration of it along harmaline had no significant effect on anxiety-like behaviors both in non-stressed and ARS mice. When harmaline and CPPG were co-administrated, CPPG potentiated the anxiolytic-like behavior induced by harmaline in non-stressed and ARS mice. The results revealed a synergistic effect between CPPG and harmaline on the induction of anxiolytic-like effect in non-stressed and ARS mice. Our results indicated an interaction between harmaline and group III mGluR on the modulation of anxiety-like responses in non-stressed and ARS mice. © 2025 Elsevier B.V.