Brain Research Bulletin, Vol. 32, pp. 443-445, 1993 0361-9230/93 $6.00 + .OO Printed in the USA. All rights reserved. Copyright 0 1993 Pergamon Press Ltd. BRIEF COMMUNICATION Effects of Intra-PVN Injections of d- and I-norephedrine on Feeding in Rats P. J. WELLMAN,’ B. DKARLO, A. MORIEN AND B. T. DAVIES Department of Psychology, Texas A&A4 University, College Station, TX 77843 Received 2 October 1992; Accepted 3 1 March 1993 WELLMAN, P. J., B. DKARLO, A. MORIEN AND B. T. DAVIES. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJI Effects zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJ of intra-PVN injections of d- and I- norephedrine on feeding in rats. BRAIN RES BULL 32(4) 443-445, 1993.-Phenylpropanolamine (PPA) is thought to inhibit feeding by activation of (Y I-adrenergic receptors within the paraventricular hypothalamus (PVN). Systemic injections of the PPA component enantiomers, d- and I-norephedrine (NEP), result in differential suppression of feeding (I-NEP more potent than d-NEP). Whether the norephedrine racemates induce differential anorexia subsequent to injection into the PVN is unknown. In the present study, adult male rats received intra-PVN injections of the d- and 1-norephedrine enantiomers (0, 80, 160, and 240 nmol). Significantly greater anorexia was obtained for I-NEP relative to d-NEP. These results document a stereospecific effect of the norephedrine enantiomers within the PVN in inhibiting food intake and suggest that the interaction ofthese enantiomers with PVN al-adrenoceptors may mediate the similar difference in potency noted for systemic injections of d- and I-norephedrine. Phenylpropanolamine Norephedrine Enantiomers Food intake INJECTION of phenylpropanolamine (PPA) into the paraven- tricular hypothalamus (PVN), but not the perifornical hypo- thalamus (PFH), significantly reduces feeding behavior in rats ( 1516). The anorexic action of PPA, a weak (Y 1 -adrenoceptor agonist (11,12), is likely due to its interaction with (Y 1 -adrenergic receptors within the PVN (14). This assertion is supported by experiments in which: a) the anorexic activity of PPA within the PVN is mimicked by other LY 1 -adrenergic agonists including phenylephrine, methoxamine, and cirazoline (4,517) and b) an- tagonism of (Y 1 -adrenergic receptors, using either systemic ad- ministration of prazosin or intra-PVN injection of benoxathian, reverse the anorexic activity of PPA and cirazoline ( 1819). PPA is a racemic mixture of the enantiomers d-norephedrine and l-norephedrine. The component enantiomers of PPA exhibit differential activity on suppressing food intake when injected systemically. A number of studies have documented that sys- temically administered I-norephedrine is three to fivefold more potent than is d-norephedrine (l-3,6,20). An interesting issue is whether this difference in potency upon systemic administra- tion reflects differential activation of PVN (Y 1 -adrenoceptors or is due to other factors such as absorption, diffusion, and/or me- tabolism of the norephedrine enantiomers. Accordingly, in the present study, adult male rats were prepared with a single cannula aimed at the PVN through which various doses (0,80, 160, and 240 nmol) of d-norephedrine (d-NEP) and I-norephedrine (l- NEP) were administered prior to tests of feeding. ’ To whom requests for reprints should he addressed. METHOD Subjects The subjects were 32 male Sprague-Dawley viral-free albino rats (obtained from Harlan Industries; Houston, TX) weighing approximately 350 g at the beginning of the study. The rats were housed individually in standard plastic rodent cages in a colony room maintained at 2 I .O + 1“C under a 12L: l2D illumination schedule (lights on at 0700 h). The rats were provided continuous access to tap water and to rodent pellets (Teklad) in the home cage. Drugs An artificial cerebrospinal fluid (CSF) consisted of 1.2 mM CaCl*, 4.0 mM KC1 and 145.8 mM NaCl dissolved in sterile distilled water. Norephedrine solutions (80, 160, and 240 nmol/ 0.5 ~1) were prepared using d-norephedrine and I-norephedrine (Aldrich Chemical) in CSF prior to injection. Norephedrine dose was calculated as the molecular weight of the base molecule. A norepinephrine solution (25 nnol/ 1.O ~1) was prepared using +- norepinephrine hvdrochloride (Sigma Chemical) with concen- tration calculated-as the weight‘oflthe base and salt. Procedure The rats were maintained in the colony room for 12 days prior to the start of the experiment to acclimate them to daily 443