Effect of ketanserin and amphetamine on nigrostriatal neurotransmission and reactive oxygen species in Parkinsonian rats. In vivo microdialysis study.
5-HT(2A/2C) receptors are one of the most important in controlling basal ganglia outputs. In rodent models of Parkinson's disease (PD) blockade of these receptors increases locomotion and enhances the actions of dopamine (DA) replacement therapy. Moreover, previously we established that 5-HT(2A/2C) antagonist attenuate DA D(1) agonist mediated vacuous chewing movements (VCMs) which are considered as an animal representation of human dyskinesia. These findings implicate 5-HT neuronal phenotypes in basal ganglia pathology, and promote 5-HT(2) antagonists as a rational treatment approach for dyskinesia that is prominent in most instances of PD replacement therapy. In the current study we determined whether ketanserin (KET) and/or amphetamine (AMPH) affected dopaminergic neurotranssmision in intact and fully DA-denervated rats. Moreover, we looked into extraneuronal content of HO. of the neostriatum after AMPH and/or KET injection, assessed by HPLC analysis of dihydroxybenzoic acids (2,3- and 2, 5-DHBA) - spin trap products of salicylate. Findings from the present study demonstrated that there are no substantial differences in extraneuronal HO. generation in the neostriatum between control and parkinsonian rats. KET did not affect DA release in the fully DA-denervated rat's neostriatum and also did not enhance HO. production. As 5-HT(2A/2C) receptor-mediated transmission might prove usefulness not only in addressing motor complications of PD patients (dyskinesia) but also in addressing non-motor problems such depression and/or L-DOPA evoked psychosis, the findings from the current study showed that the use of 5-HT(2A/2C) receptor antagonists in Parkinson's disease does not impend the neostriatal neuropil to be damaged by these drugs. We concluded that 5-HT(2A/2C) receptor antagonists may provide an attractive non-dopaminergic target for improving therapies for some basal ganglia disorders.
Nowak
P
P
Department of Pharmacology, Medical University of Silesia, Zabrze, Poland. pnowak@slam.katowice.pl
Szczerbak
G
G
Biedka
I
I
Drosik
M
M
Kostrzewa
R M
RM
Brus
R
R
D000661:Amphetamine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism
D018377:Neurotransmitter Agents; D017382:Reactive Oxygen Species; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D007650:Ketanserin; D000661:Amphetamine; D004298:Dopamine