DDAH1 and nNOS expression in the ventral tegmental area in relation to dopamine neurons

Abstract

Nitric oxide (NO) is an important signalling molecule. One-way that NO’s production is regulated is through the asymmetric dimethylarginine (ADMA)-dimethylarginine-dimethylaminohydrolase (DDAH) pathway. One role of NO in the brain is as a negative feedback signal in ventral tegmental area (VTA) dopamine (DA) neurons. It has been shown through electrophysiology that in response to depolarisation NO diffuses retrogradely and potentiates GABA release, which in turn inhibits DA neuron activity. It has been hypothesised on the basis of electrophysiology and pharmacology experiments that NO is produced by VTA DA neurons. However although both DDAH1 and nitric oxide synthase (nNOS; which is the source of neuronal NO) are expressed in the VTA, it is not clear in which cell types. I, therefore, used immunohistochemistry to investigate nNOS and DDAH1 expression in the parabrachial pigmented area (PBP) of the VTA. The PBP is where most electrophysiological recordings from DA neurons in the VTA are carried out.

I found that nNOS is expressed in the PBP of the VTA in close proximity to, but not colocalized, with DA neuron cell bodies and processes. This may indicate that NO production occurs in another cell type in response to VTA stimulation. Although DDAH1 expression was found in both DA and non-DA cells in the PBP, staining was present, although noticeably weaker, in DDAH1 global knockout mice. Thus no firm conclusion can be drawn on DDAH1 expression in the VTA.