Synergistic anxiolytic-like effect of CPPG and harmaline in non-stressed and acute restraint stress (ARS) mice

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.