The hypothalamic arcuate nucleus (ARC) is a key central neural component of the homeostatic feedback systems responsible for maintaining energy balance. Function-specific neural populations within the ARC respond to signals of central and peripheral origin indicating shifts in energy status, including noradrenergic inputs originating from brainstem nuclei. We have utilized whole-cell patch clamp recording techniques in vitro, to investigate the role of noradrenaline (NA) in regulating neuronal excitability in these neurones. Adult male Wistar rats were humanely killed by cervical dislocation, in accordance with UK guidelines, and whole-cell recordings obtained from ARC neurones in hypothalamic slices as described previously (van den Top et al., 2004). Brief (5-15s), bath application of NA (40µM) induced membrane depolarisation and increased electrical excitability in 51% (88/172) of ARC neurons, including orexigenic NPY/AgRP neurones (n=9), responses that persisted in TTX (n=12) suggesting a direct effect. NA-induced excitation was associated with increases (n=7; reversal potential -84.1 ± 5.3mV), decreases (n=5; reversal potential -24 ± 2.9mV) or no change (n=10) in conductance indicating inhibition of resting potassium and activation of non-selective cation conductances underpin these responses. Depolarising responses to NA were mimicked by phenylephrine (10µM; n=14), completely blocked by prazosin (200nM; n=16) and partly reduced by the α1a-adrenoceptor antagonist RS 100329 hydrochloride (100nM; n=14) suggesting excitation was mediated through α1-adrenoceptors, including α1a. 15% (26/172) of ARC neurones, including 4/9 putative anorexigenic cocaine-and-amphetamine regulated transcript (CART)-expressing neurones, responded to NA with hyperpolarisation and reduced excitability, the remaining CART neurones responding with excitation. 7.5% responded to NA with biphasic inhibitory/excitatory responses. NA-induced inhibition was characterised by an increase in conductance, reversal potential close to that for potassium (-83±7mV), that persisted in TTX. NA-induced inhibition was mimicked by UK-14,304 (10µM; =12) and suppressed by idazoxan (200nM; n=4), indicating a mechanism involving activation of α2-adrenoceptors coupled to a potassium conductance. Taken together these findings suggest an orexigenic role for NA in the ARC, through activation of α1 on NPY/AGRP and in part through inhibition of anorexigenic CART-expressing neurones. The functional significance of differential regulation of CART neurones requires further clarification.