Investigation of Blood-Brain Barrier Disruption in an Animal Model of Mania Induced by d-Amphetamine

Abstract Background: Bipolar disorder (BD) is a recurrent chronic psychiatric disorder. Evidence indicates that many individuals with BD exhibit high serum levels of inflammation and oxidative stress markers, which are further associated with mood symptoms and cognitive dysfunction. Due to the crosstalk between the periphery and central nervous system in BD, the disruption of the blood-brain barrier (BBB) has been proposed as a key mechanism of the pathophysiology of the disorder. This study aimed to investigate claudin-5 expression – a major protein of the BBB – in the brain of an animal model of mania induced by d-amphetamine (AMPH) and evaluate the effects of treatment with lithium. Results: AMPH-injected animals exhibited increased overall activity in the open field test. In the serum, TBARS levels were augmented in the lithium-treated groups, regardless of AMPH injection, while TNFα was not detected. In the brain, TBARS and TNFα did not differ between groups but were positively and strongly correlated in the ST of AMPH-injected rats. Contrary to the primary hypothesis, AMPH and lithium injections did not affect brain claudin-5 protein levels.Conclusions: This is one of the first attempts to investigate the effects of AMPH on BBB integrity. Although no evidence of BBB disruption was found in the current study, our results provide evidence and rationale for future research to elucidate the importance of such alteration in BD.