ISSN 18197124, Neurochemical Journal, 2012, Vol. 6, No. 2, pp. 116–120. © Pleiades Publishing, Ltd., 2012. Original Russian Text © D.N. Voronkov, E.L. Dovedova, R.M. Khudoerkov, 2012, published in Neirokhimiya, 2012, Vol. 29, No. 2, pp. 134–138. 116 1 INTRODUCTION Dysfunction of dopamine turnover plays an impor tant role in the development of neurodegenerative pro cesses in nigrostriatal structures of the brain, including the caudate nucleus and substantia nigra. Specifically, it results in the progression of Parkinson’s disease [1]. In models of dysfunction of dopamine turnover, nigrostri atal structures respond differently depending on the tar get of action. This effect has been observed due to the wide spectrum of the physiological effects of dopamine, which are related to multiple dopamine receptormedi ated mechanisms and various pathways of regulation of the activity of the dopaminergic system [2, 3]. Distur bances of dopamine turnover are associated with sub stantial changes in the balance of neurotransmitters, including acetylcholine and glutamate, which play an important role in the control of motor activity [1, 4, 5]. The schemes of the functioning of dopaminergic brain structures are not always in agreement with experimental data, which makes clarification of spe cific interactions between neurotransmitter systems in them an important task [4]. One approach to analysis of changes in the metabolism of neurotransmitters in the nigrostriatal system is the use of the drugs that influence specific stages of dopaminergic transmission differently, such as reserpine, which depletes the vesic ular mediator pool, and the antagonist of D2 dopam ine receptors, haloperidol [1, 6]. 1 Corresponding author; address: per. Obukha 5, Moscow, 105064 Russia; phone: 8 (916) 2169396; email: voronkovdm@ gmail.com. The aim of this study was to estimate changes in the activities of the enzymes involved in the metabolism of dopamine, acetylcholine, and glutamate in the nigros triatal brain structures after the longterm influence of reserpine and haloperidol. MATERIALS AND METHODS Thirty male Wistar rats weighing 180–240 g were supplied by the animal farm of the Russian Academy of Medical Sciences. The animals were housed in a vivarium with free access to water and food. The rats were divided into three equal groups. One group was injected daily intraperitoneally with a freshly prepared solution of haloperidol at a dose of 0.5 mg/kg for 14 days and the other group was injected with reser pine at a dose of 1.5 mg/kg. Both substances were dis solved in isotonic saline solution containing 0.05% Tween80 and injected in a volume of 0.5–1.0 ml. The animals of the third control group were injected intra peritoneally with the vehicle. All experiments were performed in accordance with the rules for the use of experimental animals. Sixty minutes after the last drug injection, the ani mals were decapitated under light ether anesthesia. The caudate nucleus and substantia nigra were dis sected from the brain on ice. We prepared 10% (w/w) homogenates using an extraction medium containing 0.01 M TrisHCl (pH 7.4 at 0°C), 0.32 M sucrose, and 0.001 M EDTANa 2 . The fraction of nuclei was removed by the method of differential centrifugation [7] at 1000 g for 10 min at –10°С on a K70 centrifuge Interactions between Neurotransmitter Systems in Nigrostriatal Structures of Rat Brain after LongTerm Administration of Reserpine and Haloperidol D. N. Voronkov 1 , E. L. Dovedova, and R. M. Khudoerkov Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, Russia Received April 29, 2011 Abstract—Using spectrophotometrical methods, we studied the activities of enzymes of dopamine turnover, such as tyrosine hydroxylase and monoamine oxidase B; acetylcholine turnover, such as acetylcholinesterase; and glutamate metabolism, such as glutamine synthetase in the caudate nucleus and substantia nigra of the brain of Wistar rats after a 14 day administration of reserpine and haloperidol. We found inhibition of synthesis and catabolism of dopamine and activation of the cholinergic system due to the inhibition of acetylcholine esterase. We found specific changes in the cholinergic and glutamatergic systems associated with disturbances in dopaminergic turnover after application of reserpine and haloperidol. Keywords: dopaminergic system, monoamine oxidase B, tyrosine hydroxylase, acetylcholinesterase, glutamine synthetase, substantia nigra, caudate nucleus, nigrostriatal system, haloperidol, reserpine DOI: 10.1134/S1819712412010102 EXPERIMENTAL ARTICLES