Noradrenergic modulation of ephedrine-induced hypophagia

The hypophagic action of the sympathomimetic amine ephedrine (EPH) in the rat may reflect actions on central dopaminergic (DA) and noradrenergic (NE) systems. EPH indirectly facilitates DA and NE activity and acts as a partial agonist at alpha(1)-adrenergic receptors. Two approaches were used to assess the possible contribution of NE and DA pathways to EPH-induced hypophagia. In the first, regression analyses of published archival data were computed to characterize the relation between the hypophagic potency values of (-)-(EPH) and related sympathomimetic drugs, including (+)-amphetamine, aminorex, mazindol, and phentermine (data derived from Blosser JC et al., 1987) and the most potent action of these drugs on facilitating NE activity or DA activity in rat brain (data derived from Rothman RB et al., 2001). In the NE analyses, the ED(50) values for these drugs for the inhibition of eating in rats were significantly related (r = 0.91, P = 0.03) to the potency of each drug in facilitating NE activity (either release or inhibition of [(3)H]NE reuptake), whereas in the DA analyses the correlation between ED(50) values and DA activity for these drugs was also significant (r = 0.98, P = 0.003). The regression analyses are thus supportive of a role for NE or DA in the hypophagic capacity of EPH. Although an earlier study noted that administration of the putative DA antagonist pimozide in rats attenuated EPH hypophagia, pimozide exerts similar potency in antagonizing DA receptors and alpha(1)-adrenergic receptors. To clarify the role of alpha(1)-adrenoceptors in EPH-induced hypophagia, adult male rats were pretreated with the alpha(1)-adrenergic receptor antagonist prazosin (0.0.5 and 2 mg/kg) prior to the administration of (-)-EPH (0, 5, 10, or 20 mg/kg, IP). Prazosin pretreatment at 2.0 mg/kg significantly attenuated the hypophagia, but not the hypodipsia, induced by administration of 10 mg/kg and by 20 mg/kg (-)-EPH. Collectively, these results confirm a critical contribution of of alpha(1)-adrenoceptors to the hypophagic action of (-)-EPH in rats.