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Noradrenergic modulation of ephedrine‐induced hypophagia
Author(s) -
Wellman Paul J.,
Miller Dennis K.,
Ho Dao H.
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10182
Subject(s) - pimozide , hypophagia , erythropoietin producing hepatocellular (eph) receptor , chemistry , endocrinology , medicine , potency , pharmacology , partial agonist , agonist , receptor , dopamine , haloperidol , biochemistry , in vitro , receptor tyrosine kinase
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 α 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 α 1 ‐adrenergic receptors. To clarify the role of α 1 ‐adrenoceptors in EPH‐induced hypophagia, adult male rats were pretreated with the α 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 α 1 ‐adrenoceptors to the hypophagic action of (−)‐EPH in rats. Synapse 48:18–24, 2003. © 2003 Wiley‐Liss, Inc.