**2. Norepinephrine system**

In PD, the cardinal cell death of the dopaminergic substantia nigra pars compacta (SNpc) neurons is accompanied by deficits in other monoamine neurotransmitter systems. Of these, NE appears most most consistently affected. Numerous studies, both neuroanatomical and biochemical, have documented severe loss of NE neurons, originating from the locus coeruleus (LC), concomitant with or even preceding the loss of DA neurons (Mann and Yates, 1983; Marien et al., 2004; Schapira et al., 2006). The precise anatomical relationship between the LC and the SNpc and the striatum remains to be elucidated; however, evidence exists for a functional relationship between these brain regions (Fornai et al., 2007). Most notable, loss of NE may exacerbate damage to the DA nigrostriatal system, as NE is postulated to play a neuroprotective and neuromodulator role in the progression of PD (Rommelfanger and Weinshenker, 2007). The following sections will focus on the pathophysiology of NE, its relative contribution to the development of psychiatric symptoms of PD, and the treatment of these symptoms using noradrenergic drugs.
