endofhelium. Because of recent studies showing the inhibition of experimental metastasis by sulphated polysaccharides we examined the ability of some of these polysaccharldes to inhibit EAE. Passive EAE was totally inhibited by heparin and fucoiden even when treatment of recipients was begun 3 days after transfer of cells. Penfosan and dexfran sulphate partially inhibited disease, whereas chondroiten 4 sulphate had no effect. Treatment did not merely kill the transferred cells since active sensitization at day $4 led to an early onset of disease indicating persistence of transferred cells as memory cells. Although all the inhibitory polysaccharides are anticoagulants we do not believe this alone is the reason for inhibition since a heparin preparation free of anticoagulant activity also partially inhibited EAE. Actively induced EAE was also significantly delayed by heparin treatment. The results will be discussed in terms of the polysaccharides inhibiting the movement of lymphocytes across vascular endothelium into both lymphnodes and CNS. 183 C3a ANAPHYIA-gDXIN IN THE RAT HYPOTHALAMUS POTENTIATES DI~JG-~ BEHAVIORS AND IS ANTAGONIZED BY THE DESABGINATED DERIVATIVE C3ai. Curtis Williams, Christopher Reilly, Jolynn Wagner*, Laura KeEper and Nicole Schupf*. SUNY Purchase, Purchase, N.Y. 10577 and *Manhattanville College, Purchase, N.Y. 10577. At least two C3a binding sites have been detected in the rat brain; one does not the desarginated derivative C3ai (Soc. Neurosci. Abstr. 9(2)-1213, 1983); another, which is present on a synaptosome fraction, binds C3ai as well as C3~ C3a injected into the perfornical hypothalamus (PFH) of the rat has no effect on a standard food and water intake assay, but it does potentiate norepinephrine-stimulated eating and carbachol-stimulated drinking, an effect similar to that of do[amine and also blocked by catecholamine antagonists (J. Neuroimmunol. 5:305-316, 1983). Catecholamine agonists and antagonists do not, however, compete for C3a binding sites on neural tissue or membrane preparation~ C3ai was inactive in psychopharmacological assay, but the binding data with the synaptosome fraction suggested that C3ai would antagonize the action of C3a in the PF~L Chronic cannulae to the PFH were implanted in 20 Charles River CD male rat~ Three l-ul injections were administered at 20 min. intervals; the critical series was C3ai, C3a, carbachol; water reactants in all possible combinations, were also performed. C3a activity increases carbachol-induced drinking by 50%; C3ai does not significantly affect water intake when administered alone, nor does it potentiate carbachol-induced drinking; C3ai does, however, block C3a potentiation of carbachol-induced drinking. On the basis of of membrane binding and psychopharmacolological data we propose that there are modulatory catecholamine nerve terminals in the hypothalamus whose normal functions are disrupted by C3a/C3ai-binding receptors.

C3a anaphylatoxin in the rat hypothalamus potentiates drug-induced behaviors and is antagonized by the desarginated derivative C3ai

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Page 1: C3a anaphylatoxin in the rat hypothalamus potentiates drug-induced behaviors and is antagonized by the desarginated derivative C3ai

A c t i v e l y induced EAE was a lso s i g n i f i c a n t l y delayed by hepar in t r e a t m e n t . The r e s u l t s w i l l be discussed in terms of the po l ysaccha r i des i n h i b i t i n g the movement of lymphocytes across vascu la r endothe l ium i n t o both lymphnodes and CNS.

183

C3a ANAPHYIA-gDXIN IN THE RAT HYPOTHALAMUS POTENTIATES DI~JG-~ BEHAVIORS AND IS ANTAGONIZED BY THE DESABGINATED DERIVATIVE C3ai.

Curtis Williams, Christopher Reilly, Jolynn Wagner*, Laura KeEper and Nicole Schupf*. SUNY Purchase, Purchase, N.Y. 10577 and *Manhattanville College, Purchase, N.Y. 10577.

At least two C3a binding sites have been detected in the rat brain; one does not the desarginated derivative C3ai (Soc. Neurosci. Abstr. 9(2)-1213, 1983); another, which is present on a synaptosome fraction, binds C3ai as well as C3~ C3a injected into the perfornical hypothalamus (PFH) of the rat has no effect on a standard food and water intake assay, but it does potentiate norepinephrine-stimulated eating and carbachol-stimulated drinking, an effect similar to that of do[amine and also blocked by catecholamine antagonists (J. Neuroimmunol. 5:305-316, 1983). Catecholamine agonists and antagonists do not, however, compete for C3a binding sites on neural tissue or membrane preparation~ C3ai was inactive in psychopharmacological assay, but the binding data with the synaptosome fraction suggested that C3ai would antagonize the action of C3a in the PF~L Chronic cannulae to the PFH were implanted in 20 Charles River CD male rat~ Three l-ul injections were administered at 20 min. intervals; the critical series was C3ai, C3a, carbachol; water reactants in all possible combinations, were also performed. C3a activity increases carbachol-induced drinking by 50%; C3ai does not significantly affect water intake when administered alone, nor does it potentiate carbachol-induced drinking; C3ai does, however, block C3a potentiation of carbachol-induced drinking.

On the basis of of membrane binding and psychopharmacolological data we propose that there are modulatory catecholamine nerve terminals in the hypothalamus whose normal functions are disrupted by C3a/C3ai-binding receptors.