Additive effect of histamine and muscimol upon induction of antinociceptive and antidepressant effects in mice

Abstract

We investigated the effects of histamine and GABAA receptor agents on pain and depression-like behaviors and their interaction using a tail-flick test and the forced swimming test (FST) in male mice. Our data revealed that intraperitoneal administration of muscimol (0.12 and 0.25 mg/kg) increased the percentage of maximum possible effect (%MPE) and area under the curve (AUC) of %MPE, indicating an antinociceptive response. Intraperitoneal injection of bicuculline (0.5 and 1 mg/kg) decreased %MPE and AUC of %MPE, suggesting hyperalgesia. Moreover, muscimol by reducing the immobility time of the FST elicited an antidepressant-like response but bicuculline by enhancing the immobility time of the FST caused a depressant-like response. Intracerebroventricular (i.c.v.) microinjection of histamine (5 µg/mouse) enhanced %MPE and AUC of %MPE. i.c.v. infusion of histamine (2.5 and 5 µg/mouse) decreased immobility time in the FST. Co-administration of different doses of histamine along with a sub-threshold dose of muscimol potentiated antinociceptive and antidepressant-like responses produced by histamine. Cotreatment of different doses of histamine plus a noneffective dose of bicuculline reversed antinociception and antidepressant-like effects elicited by histamine. Cotreatment of histamine, muscimol, and bicuculline reversed antinociceptive and antidepressant-like behaviors induced by the drugs. The results demonstrated additive antinociceptive and antidepressant-like effects between histamine and muscimol in mice. In conclusion, our results indicated an interaction between the histaminergic and GABAergic systems in the modulation of pain and depression-like behaviors.

Synergistic effect between citalopram and muscimol upon induction of anxiolytic- and antidepressant-like effects in male mice: An isobologram analysis

“…Some evidence indicated that GABAergic agents cause strong anxiolytic and antidepressant-like effects ( Bina et al, 2014 , Kosari-Nasab et al, 2013 ). It has been reported that the regulation of GABA A receptor signaling increases neurogenesis and reduces anxiety and depression behaviors ( Baghani et al, 2023 , Kalueff and Nutt, 2007 , Kumar et al, 2013 , Möhler, 2012 , Quadrato et al, 2014 ).…”