Open AccessStudy of reinforcing properties of new antagonists of glutamate receptors
Author(s) -
Aleksandr Mikhaylovich Potapkin,
А. А. Лебедев,
В. Е. Гмиро,
Elena V. Litasova,
Mariya A. Brusina,
Л. Б. Пиотровский,
Petr Dmitriyevich Shabanov
Publication year - 2017
Publication title -
obzory po kliničeskoj farmakologii i lekarstvennoj terapii
Language(s) - English
Resource type - Journals
eISSN - 2542-1875
pISSN - 1683-4100
DOI - 10.17816/rcf15141-47
Subject(s) - ampa receptor , phencyclidine , nmda receptor , antagonist , stimulation , pharmacology , glutamate receptor , receptor , chemistry , long term depression , sch 23390 , medicine
Reinforcing properties of antagonists of NMDA receptors IEM-1921, IEM-1791, IEM-2181 and the antagonist of AMPA receptors IEM 1460 were investigated. Substances have been synthesized in S.V. Anichkov Dept. of Neuropharmacology Institute of Experimental Medicine. Electrodes were implanted into the lateral hypothalamus for brain stimulation reward. Rats were trained to press a pedal in Skinner box for receiving electric stimulation of the brain. IEM-1921 in doses of 1, 3 and 10 mg/kg enhanced number of pedal pressing and reduced self-stimulation thresholds more than phencyclidine (in doses 1, 3, 10 mg/kg) and MK-801 (in dose 1 and 3 mg/kg). IEM-1460 in doses of 1, 3 and 5 mg/kg reduced the frequency of hypothalamic self-stimulation and enhanced it thresholds. Also we investigated the conditional reinforcing properties of antagonists of glutamate receptors in conditional place preference test (CPP). The antagonist of NMDA receptors IEM 1921 did not cause CPP. The antagonist of AMPA receptors IEM 1460 caused CPP in dose of 3 mg/kg. IEM 1791 didn’t cause CPP. At the same time IEM 2181, the IEM 1791 water-soluble salt, caused CPP. Thus, the antagonist of NMDA of receptors of IEM-1921 increases the reinforcing properties of self-stimulation in rats more than phencyclidine and MK-801.This substance can be used as means analyzer for studying of the reinforcing properties of drugs. Antagonist of NMDA receptors IEM 2181cause CPP and has the conditional reinforcing properties. It is interesting that the antagonists of AMPA receptors IEM 1460 partially cause CPP, but reduced the reinforcing properties of self-stimulation.