Study of reinforcing properties of new antagonists of glutamate receptors

Cover Page

Abstract


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.


Aleksandr M. Potapkin

Author for correspondence.
potanin@mail.ru
Institute of Experimental Medicine
Russian Federation, Saint Petersburg, Russia

post-graduate student, SV Anichkov Dept. of Neuropharmacology

Andrei A. Lebedev

aalebedev-iem@rambler.ru
Institute of Experimental Medicine
Russian Federation, Saint Petersburg, Russia

Dr Biol Sci (Pharmacology), Leading Researcher, SV Anichkov Dept. of Neuropharmacology

Valerii E. Gmiro

gmiro2119@gmail.com
Institute of Experimental Medicine
Russian Federation, Saint Petersburg, Russia

PhD (Chemistry), Leading Researcher, SV Anichkov Dept. of Neuropharmacology

Elena V. Litasova

levon-piotrovsky@yandex.ru
Institute of Experimental Medicine
Russian Federation, Saint Petersburg, Russia

PhD (Chemistry), Senior Researcher, SV Anichkov Dept. of Neuropharmacology

Mariya A. Brusina

levon-piotrovsky@yandex.ru
Institute of Experimental Medicine
Russian Federation, Saint Petersburg, Russia

Junior Researcher, SV Anichkov Dept. of Neuropharmacology

Levon B. Piotrovskii

levon-piotrovsky@yandex.ru
Institute of Experimental Medicine
Russian Federation, Saint Petersburg, Russia

Dr Biol Sci, Professor, Head of the Laboratory, SV Anichkov Dept. of Neuropharmacology

Petr D. Shabanov

pdshabanov@mail.ru
Institute of Experimental Medicine
Russian Federation, Saint Petersburg, Russia

Dr Med Sci, Professor, Head, SV Anichkov Dept. of Neuropharmacology

  • Пиотровский Л.Б., Думпис М.А., Блохина Е.А., Беспалов Ю.А. Актуальные вопросы профилактики и терапии интоксикаций. – СПб.: Астерион, 2005. – 116 с. [Piotrovsky LB, Dumpis MA, Blokhina EA, Bespalov YuA. The actual problems of intoxications prophylaxis and therapy. Saint Petersburg: Asterion; 2005. 116 p. (In Russ.)]
  • Пиотровский Л.Б., Думпис М.А., Гмиро В.Е. Достижения в области экспериментальной биологии и медицины // Институт экспериментальной медицины на рубеже тысячелетий. – СПб., 2000. – С. 13–16. [Piotrovsky LB, Dumpis MA, Gmiro VE. The success in experimental biology and medicine area. Institute of experimental medicine at millemium boundaries. Saint Petersburg; 2000. P. 13-16. (Russ.)]
  • Шабанов П.Д. Психофармакология. – СПб.: Н-Л, 2008. — 384 с. [Shabanov PD. Psychopharmacology. Saint Petersburg: N-L; 2008. 384 p. (In Russ.)]
  • Шабанов П.Д., Бородкин Ю.С. Нарушения памяти и их коррекция. – Л.: Наука, 1989. – 127 с. [Shabanov PD, Borodkin US. Memory damages and correction. Leningrad: Nauka; 1989. 127 p. (In Russ.)]
  • Шабанов П.Д., Лебедев А.А. Угнетение самостимуляции латерального гипоталамуса опиатами и опиоидами, вводимыми в центральное ядро миндалины у крыс // Рос. физиол. журн. им. И.М. Сеченова. — 2011. – Т. 97. – № 2. – С. 180–188. [Shabanov PD, Lebedev AA. Inhibition of self-stimulation of the lateral hypothalamus by opiates and opioids administered into the central amygdalar nucleus. Rossiiskii Fiziologicheskii Zhurnal Imeni IM Sechenova. 2011;97(2):180-188.
  • Шабанов П.Д., Лебедев А.А. Участие ГАМК- и дофаминергических механизмов ядра ложа конечной полоски в подкрепляющих эффектах психотропных средств, реализуемых через латеральный гипоталамус // Рос. физиол. журн. им. И.М. Сеченова. – 2011. – Т. 97. – № 8. – С. 804–813. [Shabanov PD, Lebedev AA. Participation of GABA- and dopaminergic mechanisms of the bed nucleus of stria terminalis in reinforcing effects of psychotropic drugs mediated via the lateral hypothalamus. Ross Fiziol Zh Im I M Sechenova. 2011;97(8):804-813 (In Russ.)]
  • Шабанов П.Д., Лебедев А.А. Нейрохимические механизмы прилежащего ядра, реализующие подкрепляющие эффекты самостимуляции латерального гипоталамуса // Мед. акад. журн. – 2012. – Т. 12. – № 2. – С. 68–76. [Shabanov PD, Lebedev AA. Neuro chemical mechanisms of nucleus accumbens, involved in reinforcing properties of lateral hypothalamus. Meditsinskii akademicheskii zhurnal. 2012;12(2):68-76. (In Russ.)]
  • Шабанов П.Д., Лебедев А.А., Мещеров Ш.К. Дофамин и подкрепляющие системы мозга. – СПб.: Лань, 2002. – 208 с. [Shabanov PD, Lebedev AA, Mеsherov ShК. Dopamine and reinforcing brain systems. Saint Petersburg: Lan’; 2002. 208 p. (In Russ.)]
  • Шабанов П.Д., Лебедев А.А., Ноздрачев А.Д. Гормоны гипофизарно-надпочечниковой системы в механизмах безусловного и условно-рефлекторного подкреп ления // Доклады Академии наук. – 2005. – Т. 404. – № 2. – С. 275–278. [Shabanov PD, Lebedev AA, Nozdrachev AD. Hormones of the pituitary-adrenal system in the mechanisms of unconditioned and conditioned reflex reinforcement. Dokl Biol Sci. 2005;404:329-332. (In Russ.)]
  • Шабанов П.Д., Лебедев А.А., Шевелева М.В., и др. Участие прилежащего ядра в механизмах условного подкрепления у крыс // Наркология. – 2014. – № 7. – С. 52–59. [Shabanov PD, Lebedev AA, Sheveleva МV, Shumilov ЕH, Roik RО. Involvement of nucleus accumbens into the mechanisms of conditional reinforcement in rats. Narkologia. 2014;(7):52-59. (Russ.)]
  • Шабанов П.Д., Лебедев А.А., Стрельцов В.Ф. Гормональные механизмы подкрепления. – СПб.: Н-Л, 2008. – 278 с. [Shabanov PD, Lebedev AA, Strel’tsov VF. Hormonal mechanisms of reinforcement. Saint Pe tersburg: N-L; 2008. 278 p. (In Russ.)]
  • Bolshakov KV, Kim KH, Potapjeva NN, Gmiro VE, et al. Design of antagonists for NMDA and AMPA receptors. Neuropharmacology. 2005;49(2):144-155. doi: 10.1016/ j.neuropharm.2005.02.007.
  • Carlezon WA, Thomas MJ. Biological substrates of reward and aversion: a nucleus accumbens activity hypo thesis. Neuropharmacology. 2009;56(Suppl1):122-132. doi: 10.1016/j.neuropharm.2008.06.075.
  • Weiss RD. Adherence to pharmacotherapy in patients with alcohol and opioid dependence. Addict. 2004;99:1382-1392. doi: 10.1111/j.1360–0443.2004.00884.x.

Views

Abstract - 239

PDF (Russian) - 149


Copyright (c) 2017 ECO-vector LLC

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.