A new inbred strain of Fawn-Hooded rats demonstrates mania-like behavioural and monoaminergic abnormalities

Abstract

The Fawn-Hooded (FH) rat carries a gene mutation that results in a dysfunctional serotoninergic system. However, previous studies have reported differing features between the FH/Wjd and FH/Har strains. We aimed to compare the behavioural and neurobiological features of FH/HamSlc rats with those of Fischer 344 rats. We performed the open field, elevated minus-maze, Y-maze spontaneous alternation, and forced swim tests to investigate behavioural alterations. We also assessed neurobiological characteristics by quantifying monoamines and their related compounds in the prefrontal cortex, hippocampus, and striatum using high-performance liquid chromatography with an electrochemical detection system. FH/HamSlc rats showed hyperactivity and a high impulsivity tendency in the open field and the elevated minus maze test, but no cognitive dysfunction. In addition, the hyperactivity was suppressed immediately after the forced swim test. FH/HamSlc rats showed low dopamine levels, but high dopamine turnover in the striatum. Serotonin and noradrenaline levels were low in the prefrontal cortex and the hippocampus of FH/HamSlc rats, but high serotonin turnover was observed in the prefrontal cortex, hippocampus, and striatum. FH/HamSlc rats show (1) mania-like behavioural characteristics that are different from those of other strains of FH rats; (2) stimulus dependent suppression of hyperactivity similar to the clinical findings that exercise alleviates the symptoms of bipolar disorder; and (3) monoaminergic dysregulation such as monoamine imbalance and hyperturnover that may be associated with mania-related behavioural characteristics. Thus, the FH/HamSlc rat is a new animal model for mania including bipolar disorder.

Doxycycline reverses cognitive impairment, neuroinflammation and oxidative imbalance induced by D-amphetamine mania model in mice: A promising drug repurposing for bipolar disorder treatment?

“…In line with this, Maddaloni et al (2018) showed that 5-HT depleted Tph2 mutant mice present an innate behavior resembling mania, which was reversed by mood stabilizer treatment (valproic acid) ( Maddaloni et al, 2018 ). Also, Azechi et al (2019) reported that Fawn-Hooded (FH) rats that carry dysfunctional gene mutations in the serotonergic system presented hyperactivity and high impulsivity behavior followed by low hippocampal 5-HT levels and increased 5-HT metabolization rate ( Azechi et al, 2019 ). On the other hand, the results obtained with our drug protocols revealed that DOXY had few effects against AMPH-induced 5-HT changes.…”