Evidence for functional separation of alpha-1 and alpha-2 noradrenaline receptors by pre-synaptic terminal re-uptake mechanisms

Information transfer within the central nervous system is predominantly chemical in nature, and occurs both through synaptic specialisations and non-specific diffuse release. The localisation and description of receptors for these two types of neurotransmission is currently a contentious issue. In the present study, the noradrenaline reuptake inhibitor cocaine has been shown to overcome the inhibitory effects of idazoxan, a selective alpha-2 receptor antagonist, but not phentolamine, a non-selective alpha receptor antagonist, on eating following injection of noradrenaline into the rat hypothalamic paraventricular nucleus. Similarly, lesion by 6-hydroxydopamine of noradrenaline terminals in the paraventricular nucleus also reduced the efficacy of idazoxan in blocking eating induced by noradrenaline. These data confirm that post-synaptic alpha-2 receptors are involved in the feeding response to exogenous noradrenaline, but in addition, when taken in conjunction with previously published data, are used to suggest a differential distribution of NA receptors within the hypothalamic paraventricular nucleus. It is proposed that the alpha-2 subtype may be extrasynaptic, the alpha-1 subtype intrasynaptic.