| Author/Editor | Glavan, Gordana | |
| Title | Genska ekspresija kot kazalec učinka ergolinskega derivata LEK-8829 na dopaminske receptorje pri podganah z enostransko poškodbo nigrostriatne poti | |
| Type | monografija | |
| Place | Ljubljana | |
| Publisher | Univerza v Ljubljani, Medicinska fakulteta | |
| Publication year | 2000 | |
| Volume | str. 89 | |
| Language | slo | |
| Abstract | Previous experiments have suggested a potential antipsychotic activity of the ergoline derivative LEK-8829. In vitro experiments showed a high affinity to 5-HT2, 5-HT1A in D-2 receptors and moderate affinity to D-1 receptors. High ratios of affinities to 5-HT2: D-2 receptors allowed classification of LEK-8829 among atypical antipsychotics. In vivo experiments showed antagonism of D-2 and 5-HT receptor-linked behaviours. The behavioural studies using rats with unilateral lesions of dopamine nigrostriatal neurons with 6-hydroxydopamine (6-OHDA model) revealed agonistic effect of LEK-8829 on D-1 supersensitive receptors and antagonistic effect on D-2 supersensitive receptors. In the present study, 6-OHDA model was used to determine the activity of LEK-8829 on dopamine receptors by observing turning behaviour and striatal proenkephalin, preprotachykinin, neurotensin and ania-4 mRNA levels. The administration of LEK-8829 induced contralateral turning behaviour that was prevented by pretreatment with SCH-23390, the specific D-1 receptor antagonist. The contralateral turning induced by quinpirole (specific D-2 receptor agonist) was inhibited by coadministration of SCH-23390 and LEK-8829. These data confirmed agonistic activity of LEK-8829 on D-1 supersensitive receptors and its antagonistic activity on D-2 supersensitive receptors. The brains of the rats from behavioural experiments were used for in situ hybridization in order to determine the effects of LEK-8829 on gene expression in striatum. LEK-8829 showed agonistic effect on supersensitive and normosensitive D-1 receptors. Namely, LEK-8829 elevated the expression of neurotensin and ania-4 mRNA in the denervated and innervated striatum that was blocked by the pretreatment with SCH-23390. (Abstract truncated at 2000 characters.) | |
| Descriptors | BEHAVIOR, ANIMAL ERGOLINES CORPUS STRIATUM RECEPTORS, DOPAMINE D1 RECEPTORS, DOPAMINE D2 RATS HYDROXYDOPAMINES MOVEMENT QUINPIROLE RNA, MESSENGER NEUROTENSIN GENE EXPRESSION ENKEPHALINS TACHYKININS IN SITU HYBRIDIZATION |