Open AccessThe inhibitory effects of orexin antagonists on the reinforcing properties of amphetamine during brain self-stimulation and the development of a conditioned place preference in rats
Author(s) -
Petr D. Шабанов,
Шабанов Петр Дмитриевич,
Sergei Vladimirivich Azarenko,
Азаренко Сергей Владимирович,
Vitalii I. Morozov,
Морозов Виталий Иванович,
Yulia N. Bessolova,
Бессолова Юлия Николаевна,
А. А. Лебедев,
Лебедев Андрей Андреевич
Publication year - 2020
Publication title -
obzory po kliničeskoj farmakologii i lekarstvennoj terapii
Language(s) - English
Resource type - Journals
eISSN - 2542-1875
pISSN - 1683-4100
DOI - 10.17816/rcf17457-64
Subject(s) - orexin , lateral hypothalamus , conditioned place preference , stimulation , orexin receptor , medicine , endocrinology , agonist , orexin a , brain stimulation reward , amphetamine , chemistry , pharmacology , neuropeptide , receptor , dopamine , nucleus accumbens
Purpose. In experiments on rats, we studied the self-stimulation reaction of the lateral hypothalamus and the conditioned reaction of place preference upon activation (orexin) and blockade of the orexin receptor by SB-408124 or Orexin B18-28 in rats.
Methods. As behavioral methods, self-stimulation of the lateral hypothalamus and a conditioned reaction of place preference were chosen. Orexin and its antagonists SB-408124 or Orexin B18-28 (Sigma, USA) were used for pharmacological analysis. All preparations were used in 3 dosages: 0.1, 1.0, 10 g, injecting into the lateral ventricle of the brain (i.v.) through the implanted cannula.
Results. It has been shown that peptide substances of orexin and its antagonists modulate the conditional and unconditional reinforcing properties of the brain. The studied orexin antagonists showed a dose-dependent (0.1-1-10 g, i.v.) inhibitory effect on the self-stimulation of the lateral hypothalamus, activated by indirect adrenergic agonist amphetamine (-phenylisopropylamine). The inhibitory effect of orexin antagonists also manifested itself in relation to the generation and expression of a preference for amphetamine place, especially when using high doses of the peptide (10 g i.v.).
Conclusion. The effect of orexin antagonists can be used in the development and study of antinarcotic drugs.