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1

Effect of combined prenatal exposure to aluminium and ethanol on central dopamine, serotonin and muscarine receptor reactivity in rats

100%

Brus R. , Szkilnik R. , Nowak P. , Mikolajun U. , Tramer W. , Mengel K.

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nr 2

EN

Ethanol (EtOH) abuse in pregnancy is know to seriously damage the internal organs of the fetus, a condition in humans that is classified as "fetal alcohol syndrome". Aluminium (Al) can develop neurotoxic effects and contribute to some neurological disorders. To test whether the reactivity of some central receptors (dopamine - DA, serotonin-5-HT and muscanne - M) may be altered by prenatal EtOH and Al, administered separately or jointly, female rats were given 10% (v/v) EtOH and/or Al(600 or 3000 ppm) throughout pregnancy in their drinking water. Male adult offspring were tested at 3 months for behavioural effects know to be induced by agonists acting at different subtypes of DA (D1 D2, D3,), 5-HT2t and M receptors. Addition antagonist of D, receptor have been examined. The substances SKF 38393, quinpirole, mCPP, pilocarpine, haloperidol, and the behavioral procedures of yawning, oral activity and catalepsy have been used for assessment. The results of the experiment indicate that EtOH does not modify the effect of the central DA and M receptor agonist and DA antagonist in Al prenataly exposed rats. On the other hand, EtOH modified the reactivity of the central 5-HT2c receptor to agonist (mCPP) in Al pretreated rats.

2

An influence of lesions of the catecholaminergic cerebellar innervation on the harmaline-induced tremor in rats

84%

Wardas J. , Kolasiewicz W. , Kuter K. , Berghauzen K. , Nowak P. , Mikolajun U. , Zapala M. , Ossowska K.

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tom 73

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nr 1

EN

Recent studies have suggested a crucial role of the cerebellum in different forms of tremor. Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway and Purkinje cells results in the essential tremor in humans and the harmaline-induced tremor in animals. Moreover, an increased neuronal activity of the cerebellum has been found to contribute to the tremor in Parkinson’s disease (PD). Since the cerebellum receives dopaminergic and noradrenergic pathways arising from regions affected in PD, the aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervation to the harmaline-induced tremor in rats. Rats were bilaterally injected into the cerebellar vermis (lobules 8–10) with 6-hydroxydopamine (6-OHDA) (8 μg/0.5 μl) either alone or this treatment was preceded by desipramine (15 mg/kg i.p.). Harmaline was administered at a dose of 7.5 mg/kg i.p. on the 9th post-operative day. Tremor of forelimbs was measured as a number of episodes. After completion of behavioural experiments rats were killed by decapitation and the levels of monoamines and their metabolites were measured by HPLC in lobules 1–3, 4–7 and 8–10 of the cerebellum. 6-OHDA injected alone decreased the noradrenaline level by ca. 40–80% in the cerebellum and enhanced the harmaline-induced tremor. When 6-OHDA administration was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum but induced its compensatory activation in others. Finally no influence of the latter treatment on the tremor induced by harmaline was observed. The present study indicates that the noradrenergic innervation of the cerebellum plays an inhibitory role in the harmaline-induced tremor. The study was supported by the grant of the Ministry of Science and Higher Education No N N401 570638, and partly by Statutory Funds of the Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland.

3

6-OHDA-induced lesion of a8-a9 dopaminergic neurons increases the harmaline-induced tremor in rats

84%

Kuter K. , Berghauzen K. , Wardas J. , Kolasiewicz W. , Nowak P. , Zapala M. , Mikolajun U. , Ossowska K.

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tom 73

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nr 1

EN

Degeneration of dopaminergic nigrostriatal pathway is generally accepted to be a cause of Parkinson’s disease (PD) motor symptoms such as akinesia, bradykinesia and tremor. Unfortunately the extent of the degeneration does not correlate with tremor occurrence and intensity, therefore cannot explain sufficiently its appearance. Mechanisms leading to induction of tremor are still not explained. Interestingly, image analysis studies have suggested contribution of an increased activity of the cerebellum to the PD tremor. The aim of the present study was to examine whether a selective, partial lesion of dopaminergic structures – the substantia nigra pars compacta (SNc, A9) and retrorubral field (RRF, A8) would influence the tremor behaviour induced by harmaline. Harmaline model of tremor induces an abnormal synchronous activation of the climbing glutamatergic olivo-cerebellar pathway and cerebellar Purkinje cells. 6-OHDA (8 mg /2 ml) was injected unilaterally into the region of the posterior part of the SNc and RRF to induce moderate size of degeneration, similar to early PD. Harmaline was administered in a dose of 7.5 mg/kg i.p. on the 8th day after the operation and tremor of forelimbs, head and trunk was measured. In precise behavioural studies we have found that the lesion of dopaminergic system increased intensity of the tremor induced by harmaline but did not influence its character. Stereological examination of the lesion extent revealed losses of dopaminergic (tyrosine hydroxylase-immunoreactive) neurons in the anterior (30%) and posterior (72%) SNc, as well as in RRF (72% on the average). Levels of dopamine and all its metabolites, as well as noradrenaline concentrations on ipsilateral to lesioned side were moderately decreased in the caudate-putamen, while, dopamine and DOPAC in the anterior cerebellum were increased. In the caudate-putamen, the ipsi/contra ratio of dopamine level correlated negatively, while that of dopamine turnover positively with the tremor intensity. However, in the anterior cerebellum an inverse relationship was found. Moreover, this symptom correlated positively with serotonin level and negatively with the 5-HIAA/serotonin ratio on the contralateral side of the posterior cerebellum. The presented results indicate that modulation of dopaminergic and serotonergic transmissions by the dopaminergic system lesion, modelling early stages of PD, may influence cerebellar mechanisms triggering tremor. The study was supported by the grant of the Ministry of Science and Higher Education No N_N401_570638 and by Statutory Funds of the Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Cracow, Poland