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

Hirotsugu Azechi,Kōsuke Hakamada,Takanobu Yamamoto

doi:10.1016/j.ibror.2019.11.001

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.

Highlights

Fawn-Hooded (FH) rats have a gene mutation in the recessive redeyed dilution gene on chromosome 1, which is responsible for dysfunctional 5-hydroxytryptamine (5-HT) release from platelets (Tschopp and Zucker, 1972)
Our results show that the FH/HamSlc strain exhibits mania-like traits in behavioural and neurobiological analyses, which indicates that it could be used as a model for mania including bipolar disorder
Our behavioural analysis revealed that FH/HamSlc rats are more hyperactive in the open field (Fig. 1B), spontaneous alternation (Fig. 3B), and forced swim (Fig. 4A) tests

Summary

Introduction

Fawn-Hooded (FH) rats have a gene mutation in the recessive redeyed dilution gene on chromosome 1, which is responsible for dysfunctional 5-hydroxytryptamine (5-HT) release from platelets (Tschopp and Zucker, 1972). Hypertension and renal impairments have been attributed to Bpfh-1, and to Rf-1 and Rf-2, respectively, in FH rats These genes are close to the red-eyed dilution (Brown et al, 1996; Prieur and Meyers, 1984). Overstreet et al reported that FH/Wjd rats show higher basal corticosterone levels and longer immobility times in the forced swim test, and that these abnormalities are normalised following antidepressant treatment, suggesting that the FH rat may be useful as an animal model of depression (Overstreet et al, 1992; Rezvani et al, 2002). Lahmame et al (1996) showed that FH/Har rats exhibit hyperactivity in some behavioural analyses and no change in corticosterone levels in response to tail-cut stress, indicating that the FH rat may not be an appropriate model of depressive disorder. A direct comparison study between FH/Wjd and FH/Har rats has demonstrated that FH/Wjd rats exhibit longer immobility times than

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