Experimental Studies of the Effects of the Dopamine D 2 Receptor Agonist Cabergoline on Catecholamine Content and BDNF m
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Experimental Studies of the Effects of the Dopamine D2 Receptor Agonist Cabergoline on Catecholamine Content and BDNF mRNA Expression in the Midbrain and Hypothalamus P. K. Anokhin,1 A. G. Veretinskaya,1 V. V. Pavshintsev,2 and I. Yu. Shamakina1
Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 119, No. 11, Iss. 1, pp. 54–59, November, 2019. Original article submitted May 21, 2019. Accepted July 31, 2019. Objectives. To study the effects of cabergoline on the catecholamine content and brain-derived neurotrophic factor (BDNF) mRNA expression in the midbrain and hypothalamus. Materials and methods. Experiments were performed on 20 adult male Wistar rats. Animals of the experimental group (n = 10) received i.p. cabergoline (0.5 mg/kg). Control animals (n = 10) received the same volume of solvent. Dopamine and noradrenaline contents were measured by high-performance liquid chromatography with electrochemical detection and the relative BDNF mRNA level was analyzed using the real-time polymerase chain reaction after reverse transcription. Results and conclusions. Administration of cabergoline was followed 24 h later by a significant increase in the noradrenaline content in the midbrain of animals of the experimental group as compared with the control group (639.2 ± 64.5 ng/g vs. 398.0 ± 66.0 ng/g, p < 0.05), while there was no change in the dopamine level (211.4 ± 16.3 ng/g vs. 169.7 ± 54.6 ng/g). No Changes in transmitter contents in the hypothalamus were seen. Administration of cabergoline led to a two-fold increase in the BDNF mRNA level in the midbrain but not in the hypothalamus at 24 h after injection. Keywords: dopamine, catecholamine, D2 receptors, cabergoline, BDNF.
The type 2 dopamine receptor (D2R) agonist cabergoline is currently used in neurology and neuroendocrinology, mainly in the treatment of Parkinson’s disease (PD) [1], restless legs syndrome [2], Cushing’s disease [3], and hyperprolactinemia of various causes [4]. Cabergoline is an ergot derivative, i.e., a D2R ergoline agonist, a group which also includes bromocriptine, lisuride, and pergolide [5]. The unique property of cabergoline, distinguishing it from other members of this group, is its long half-elimination time (63–109 h) [1] and, thus, its longer-lasting therapeutic effect after single doses. Experimental studies have shown that systemic administration of cabergoline decreases alcohol consumption in chronically alcoholized animals [6, 7]. An interesting finding was the experimental detection of the antidepressant and anxiolytic properties of cabergo-
line in classical tests for anxiety in rodents (forced swimming, open field, elevated maze, model of impaired feeding behavior) [8]. The previously unknown properties of cabergoline, along with the high comorbidity of dependence diseases and anxiety and depressive disorders [9, 10], suggest the existence of a common target for cabergoline by which it mediates its effects. Normalization of the behavior of animals in models of experimental depression on administration
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