The aim of the present study was to examine the influence of the long-term paraquat administration on the dopaminergic nigrostriatal system in rats. Paraquat was injected at a dose of 10 mg/kg i.p. for 4-24 weeks. We found that this pesticide reduced the number of tyrosine hydroxylase-immunoreactive neurons of the substantia nigra; after the 4-week treatment the reduction (17%, nonsignificant) was confined to the rostrocentral region of this structure but, after 24 weeks, had spread along its whole length and was approximately 37%. Moreover, it induced a biphasic effect on dopaminergic transmission. First, levels of dopamine, its metabolites and turnover were elevated (4-8 weeks) in the caudate-putamen, then all these parameters returned to control values (12 weeks) and dropped by 25-30% after 24 weeks. The binding of [3H]GBR 12,935 to dopamine transporter in the caudate-putamen was decreased after 4-8 weeks, then returned to control values after 12 weeks but was again decreased after 24 weeks. Twenty-four-week paraquat administration also decreased the level of tyrosine hydroxylase (Western blot) in the caudate-putamen. In addition, paraquat activated serotonin and noradrenaline transmission during the first 12 weeks of treatment but no decreases in levels of these neurotransmitters were observed after 24 weeks. The above results seem to suggest that long-term paraquat administration produces a slowly progressing degeneration of nigrostriatal neurons, leading to delayed deficits in dopaminergic transmission, which may resemble early, presymptomatic, stages of Parkinson's disease.

No abstract

No abstract

No abstract

No abstract

No abstract

The aim of this article was to review the recent literature on the role of excitatory amino acids in Parkinson's disease and in animal equivalents of parkinsonian symptoms. Effects of NMDA and AMPA antagonists on the reserpine-induced akinesia, catalepsy and rigidity, on the neuroleptic-induced catalepsy, on the turning behaviour of 6-OHDA-lesioned rats, as well as on the parkinsonian symptoms evoked by MPTP in monkeys were analysed. Moreover, the role of NMDA antagonists in Parkinson's disease was discussed. Data concerning the protective influence of these drugs on degenerative properties of methamphetamine, MPTP and 6-OHDOPA were also presented. On the basis of the above findings, the following conclusions may be drawn: (1) disturbances in the glutamatergic transmission in various brain structures seem to play a significant role in the development of symptoms of Parkinson's disease; (2) the NMDA-receptor blocking component may make a substantial contribution to the therapeutic effect of antiparkinsonian drugs; a similar contribution of AMPA-receptor blocking component has not been sufficiently documented, so far; (3) compounds blocking NMDA receptors may possibly prevent the development of Parkinson's disease; this presumption needs, however further studies; (4) side effects of NMDA receptor antagonists may be a limiting factor in the use of these compounds in humans.

The aim of this study was to examine whether (+)-2-aminobicyclo[3.1.0]-hexane-2,6-dicarboxylate monohydrate (LY354740), a selective agonist of group II metabotropic glutamate receptors, possesses antiparkinsonian properties. Parkinsonian-like muscle rigidity was induced by pretreatment with haloperidol (1 mg/kg i.p.). It was measured as increased resistance developed by the rat's hind leg to passive extension and flexion. LY354740 (5 and 10 mg/kg i.p.) dose-dependently diminished the haloperidol-induced muscle rigidity. The present results suggest that LY354740 counteracts the muscle rigidity in an animal model of parkinsonism.