Investigation of the therapeutic efficacy of valproic acid on neurotransmitter network and TRPC 3/6 signaling in a quinpirrole-induced mouse model of obsessive compulsive disorder

Obsessive Compulsive Disorder (OCD) is a chronic neuropsychiatric disorder that affects the individual throughout life, often with disabling symptoms in daily life. In our study, we aimed to investigate the therapeutic effects of valproic acid on TRPC 3/6 in different brain tissues in OCD model induced by quinpirole (QNP), a D2 dopamine (DP) receptor agonist in mice. A total of 24 Balb/c male mice were divided into 4 groups as control (K), VPA, QNP (0.2 mg/kg every four days), QNP+VPA, with 6 animals in each group. QNP was administered subcutaneously every day for 19 days to establish the model. At the end of 12 days, VPA-induced treatment was started by oral gavage. For 19 days, "Compulsive Sucrose Drinking and Home Base Preference Test" was applied. Then, open field, elevated plus maze, marble burying, novel object recognition and sucrose drinking tests related to OCD and anxiety were administered. The animals were then decapitated and mRNA levels of TRPC 3/6-related genes in cerebral cortex, striatum and hippocampus tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), reactivity of TRPC 3/6 in hippocampus and striatum tissues by immunohistochemistry and DP, serotonin (ST), BDNF and GDNF levels in total brain were evaluated by ELISA method. By affecting TRPC channel expression, VPA modulates intracellular calcium signaling pathways that are crucial for synaptic plasticity and neuronal excitability. This effect of VPA on neuroplasticity potentially normalizes the dysregulated neuronal circuits involved in OCD, especially through the functional interaction of TRPC 3 and TRPC 6 channels. We have explained synchronously with behavioral, biochemistry, immunohistochemistry and molecular methods that the appropriate neuronal signal is restored and reduces anxiety and compulsive-like behaviors. According to literature data, the present study was conducted in a QNP model of OCD in Balb/c mice using valproic acid in TRPC 3/6 is the first study evaluating the therapeutic effects of valproic acid through signaling. Treatment efficacy of valproic acid observed It is likely to exert a therapeutic effect via TRPC 3/6 in the cortico-striato-thalamo-cortical circuit.