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Copyright © 1998 by Institute of Pharmacology Polish Academy of Sciences |
Pol. J. Pharmacol., 1998, 50, 399-406 ISSN 1230-6002 |
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Effect of local intracerebral administration of EMD 57445, a selective sigma receptor ligand, on the locomotor activity of the rat.
G. SKUZA, W. KOLASIEWICZ, M. DZIEDZICKA-WASYLEWSKA, W. MARGAS. Pol. J. Pharmacol.,1998, 50, 399-406. EMD 57445 is a new compound which has been characterized by high affinity for sigma receptor sites. It has not been shown to bind to any other receptors, including dopamine ones. However, hitherto existing data (behavioral as well as biochemical) have suggested that this drug exhibits functional antidopaminergic activity. Therefore, in the present study, the local cerebral administration of EMD 57445 has been used in order to better elucidate the actual site of action of this compound in the central nervous system. EMD 57445 given unilaterally into the nucleus accumbens, striatum and lateral ventricle decreases the locomotor activity of the rats, the effect being the most pronounced in the case of administration into the nucleus accumbens. Moreover, unilateral intraaccumbal injection of EMD 57445 significantly diminishes apomorphine (given peripherally)-induced hyperactivity. Local administration of EMD 57445 into the prefrontal cortex of the rats also attenuated the locomotor activity but the effect was statistically significant only after bilateral administration of the compound. Additionally, the lack of influence of EMD 57445, administered po, on the dopamine D1 and D2 receptor binding in the striatal membranes was observed in these studies. However, in limbic forebrain the density of D2 receptors decreased after the higher dose of EMD 57445. In conclusion, the results obtained in this paper support the hypothesis that EMD 57445 exerts antidopaminergic activity through indirect inhibition of dopamine system. Key words: EMD 57445, intracerebral injections, locomotor activity, D1-, D2-receptor binding, sigma receptor, rat |
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