| Avtor/Urednik | Šprah, Lilijana; Živin, Marko; Sket, Dušan | |
| Naslov | Ergoline derivative LEK-8829-inducet turning behavior in rats with unilateral striatal ibotenic acid lesions: interaction with bromocriptine | |
| Tip | članek | |
| Vir | J Pharmacol Exp Ther | |
| Vol. in št. | Letnik 288, št. 3 | |
| Leto izdaje | 1999 | |
| Obseg | str. 1093-100 | |
| Jezik | eng | |
| Abstrakt | LEK-8829 (9, 10-didehydro-N-methyl-(2-propynyl)-6-methyl-8-aminomethylergoline bimaleinate) is an antagonist of dopamine D2 receptors and serotonin (5-HT)2 and 5-HT1A receptors in infact animals and a D1 receptor agonist in dopamine-depleted animals. In the present study, we used rats with unilated striatal lesions with ibotenic acid (IA) to investigate the dopamine receptor activities of LEK-8829 in a model with innervated dopamine receptors. The IA-lesioned rats circled ipsilaterally when challenged with apomorphine, the mixed agonist on D1/D2 receptors. LEK-8829 induced a dose-dependent contralateral turning that was blocked by D, receptor antagonist SCH-23390. The treatment with D1 receptor agonist SKF-825958 induced ipsilateral turning, whereas the treatment with D2 receptor antagonist haloperidol induced contralateral posture. The combined treatment with SKF-82958 and haloperidol resulted in a weak contralateral turning, indicating the possible receptor mechanism of contralateral turning induced by LEK-8829. Bromocriptine induced a weak ipsilateral turning that was blocked by haloperidol. The ipsilateral turning induced by bromocriptine was significantly potentiated by the coadministration of a low dose but not by a high dose of LEK-8829. The potentiation of turning was blocked either by SCH-23390 or by haloperidol. The potentiation of ipsilateral turning suggests the constimulation of D2 and D1 receptors by bromocriptine and LEK-8829, respectively, whereas the lack of potentiation by the highest dose of LEK-8829 may be explained by the opposing activity of LEK-8829 and bromocriptine at D2 receptors. We propose that the D2 and 5HT2 receptor-blocking and D1 receptor-stimulating profile of LEK-8829 is promising for the treatment of negative symptoms of schizophrenia. | |
| Deskriptorji | HALOPERIDOL SCH-23390 CORPUS STRIATUM RECEPTORS, DOPAMINE RECEPTORS, SEROTONIN BROMOCRIPTINE APOMORPHINE RATS, WISTAR PSYCHOTHERAPY SCHIZOPHRENIA IBOTENIC ACID |