Abstract
Monoaminergic neurotransmission is greatly dependent on the function of the vesicular monoamine transporter VMAT2, which is responsible for loading monoamines into secretory vesicles. The role of VMAT2 in histaminergic neurotransmission is poorly understood. We studied the structure and function of the histaminergic system in larval zebrafish following inhibition of VMAT2 function by reserpine. We found that reserpine treatment greatly reduced histamine immunoreactivity in neurons and an almost total disappearance of histamine-containing nerve fibers in the dorsal telencephalon and habenula, the most densely innervated targets of the hypothalamic histamine neurons. The reserpine treated larvae had an impaired histamine-dependent dark-induced flash response seen during the first second after onset of darkness, implying that function of the histaminergic network is VMAT2 dependent. Levels of histamine and other monoamines were decreased in reserpine treated animals. This study provides conclusive evidence of the relevance of VMAT2 in histaminergic neurotransmission, further implying that the storage and release mechanism of neural histamine is comparable to that of other monoamines. Our results also reveal potential new insights about the roles of monoaminergic neurotransmitters in the regulation of locomotion increase during adaptation to darkness.
Highlights
The function of most monoamine neurotransmitters is dependent on the vesicular release made possible by the vesicular monoamine transporter 2 (VMAT2)
We found that histamine immunoreactivity in the brain was strongly diminished by reserpine treatment both in neuronal cell bodies and, more importantly, their projections in key target areas in the dorsal telencephalon and habenula
The number of neurons preserved was similar in both treatment groups and all time points observed, with the number of cells showing clear histamine immunoreactivity decreased by about 40% following reserpine treatment
Summary
The function of most monoamine neurotransmitters is dependent on the vesicular release made possible by the vesicular monoamine transporter 2 (VMAT2). Depression has often been reported as a side-effect of reserpine treatment, which was a key factor in the development of the monoamine depletion theory of depressive disorders and the reserpine treated animal model for depression, the monoamine hypothesis has recently been challenged[4,5,6]. Taken together, these findings underline the significance of monoamine dependent neurotransmission in brain physiology. Reserpine has been shown to inhibit L-histidine induced increase in brain histamine in rats and mice[10, 15].
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