Modulation of the reinforcing effects of psychotropic drugs by means of GABA- and dopaminergic mechanisms of the bed nucleus of stria terminalis

Abstract


The purpose of the investigation was to clear the significance of GABA and dopamine systems of the bed nucleus of stria terminalis for the reinforcing effects of a number of psychotropic drugs (opiates, opioids, psychostimulants) on self-stimulation of the lateral hypothalamus in rats. The Wistar male rats were implanted bipolar electrodes in the lateral hypothalamus to study self-stimulation reaction in the Skinner box. Simultaneously, the microcannules were implanted into the bed nucleus of stria terminalis to inject the drugs studied (1 μg in 1 μl in volume for each injection). The blockade of GABA a receptors (bicuculline 1 μg), sodium influx ionic currents (xycaine, or lidocain 1 μg) or D 1 dopamine receptors (SCH23390) by means of intrastructural administration of drugs into the bed nucleus of stria terminalis decreased, but the blockade of D 2 dopamine receptors (sulpiride) mildly increased self-stimulation reaction of the lateral hypothalamus in rats. The inhibition degree of self-stimulation was the following range: xycaine > SCH23390 = bicuculline (the drugs are located in the range of descending inhibition activity). On the background of blockade of GABA a receptors (bicuculline) in the bed nucleus of stria terminalis, only sodium ethaminal reproduced its psychostimulant effect, but amphetamine, fentanyl and leu-enkephaline did not appear it. The blockade of D 1 dopamine receptors with SCH23390 prevented the reinforcing effects of all narcogenic drugs. On the opposite side, the intrastructural administration of xycaine into the bed nucleus of stria terminalis strengthened the effects of amphetamine, fentanyl and leu-enkephaline without the effect of sodium ethaminal. At the same time, the blockade of D 2 dopamine receptors with sulpiride increased self-stimulation and strengthened positive reinforcing effects of sodium ethaminal and leu-enkephaline without effects of amphetamine and fentanyl. Therefore, the bed nucleus of stria terminalis controls the hypothalamic self-stimulation via GABA- and dopaminergic mechanisms. GABA realizes the negative (inhibitory) action. The direct positive (activating) effect on the lateral hypothalamus is realized through D 1 dopamine receptors, and D 2 dopamine receptors of the bed nucleus of stria terminalis limit the positive effects of narcogenic drugs.

P D Shabanov

Military Medical Academy, St. Petersburg

Email: pdshabanov@mail.ru

A A Lebedev

Institute of Experimental Medicime, North West Branch, Academy of Medical Sciences, St. Petersburg

  1. Лебедев A.A., Шабанов П.Д. Сопоставление реакции самостимуляции и условного предпочтения места при введении фенамина у крыс // Журн. высш. нервн. деят. 1992. Т. 42. № 4. С. 692-698.
  2. Шабанов П.Д. Психофармакология. СПб., 2008. 384 с.
  3. Шабанов П.Д., Лебедев A.A. Структурно-функциональная организация системы расширенной миндалины и ее роль в подкреплении // Обзоры по клин. фармакол. и лек. терапии. 2007. Т. 5. № 1. С. 2-16.
  4. Шабанов П.Д., Лебедев A.A., Мещеров Ш.К. Дофамин и подкрепляющие системы мозга. СПб.: Лань, 2002. 208 с.
  5. Шабанов П.Д., Лебедев A.A., Воеводин Е.Е., Стрельцов В.Ф. Блокада рецепторов кортиколиберина в миндалине астрессином устраняет подкрепляющие эффекты фенамина, морфина и лей-энкефалина на самостимуляцию мозга // Эксп. и клин. фармакол. 2006. Т. 69. № 3. С. 14-18.
  6. Шабанов П.Д., Лебедев A.A., Стрельцов В.Ф. Гормональные механизмы подкрепления. СПб., 2008. 208 с.
  7. Шабанов П.Д., Лебедев A.A., Русановский В.В., Стрельцов В.Ф. Поведенческие эффекты корти колиберина и его аналогов, вводимых в желудочки мозга крыс // Мед. акад. журн. 2005. Т. 5. № 3. С. 59-67.
  8. Шабанов П.Д., Сапронов Н.С. Психонейроэндокринология. СПб.: Информ-Навигатор, 2010. 984 с.
  9. Шаляпина В.Г., Шабанов П.Д. Основы нейроэндокринологии. СПб.: Элби-СПб, 2005. 472 с.
  10. Alheid G.F., Heimеr L. Theories of basal forebrain organization and the “emotional motor system” // Progr. Brain Res. 1996. Vol. 107. P. 461-484.
  11. Bruijnzeel A.W., Gold M.S. The role of corticotrophin-releasing factor-like peptide4s in cannabis, nicotine, and alcohol dependence // Brain Res. Rev. 2005. Vol. 49. P. 505-528.
  12. Koob G.F. Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory // Pharmacopsychiatry. 2009. Vol. 42 (Suppl. 1). P. S32-S41.
  13. Koob G.F. Neurobiological substrates for the dark side of compulsivity in addiction // Neuropharmacology. 2009. Vol. 56 (Suppl. 1). P. 18-31.
  14. König K.P., Klippel A.A. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Baltimore. 1963.214 p.
  15. Samyai Z., Shaham Y., Heinrichs S.C. The role of corticotropin-releasing factor in drug addiction // Pharmacol. Rev. 2001. Vol. 53. P. 209-243.
  16. Shabanov P.D. The extended amygdala CRF receptors regulate the reinforcing effect of self-stimulation // Int. J. Addiction Res. 2008. Vol. 1. № 1. P. 200-204.
  17. Shabanov P.D., Lebedev A.A., Nozdrachev A.D. Extrahypothalamic corticoliberin receptors regulate the reinforcing effects of self-stimulation // Dokl. Biol. Sci. 2006. Vol. 406. P. 14-17.
  18. Swanson L.W., Petrowich G.D. What is the amygdala? // Trends Neurosci. 1998. Vol. 21. P. 323-331.
  19. Velley L. The role of intrinsic neurons in lateral hypothalamic selfstimulation // Behav. Brain Res. 1986. Vol. 22. №2. P. 141-152.
  20. Waraczynski M. Lidocaine inactivation demonstrates a stronger role for central versus medial extended amygdala in medial forebrain bundle self-stimulation // Behav. Brain Res. 2006. Vol. 173. № 2. P. 288-298.
  21. Waraczynski M. GABA receptor agonism in the sub-lenticular central extended amygdala impairs medial forebrain bundle self-stimulation but GABA blockade does not enhance it // Behav. Brain Res. 2008. Vol. 187. № 2. P. 396-404.
  22. Waraczynski M., Salemme J., Farral B. Brain stimulation reward is affected by D2 dopamine receptor manipulations in the extended amygdala but not the nucleus accumbens // Behav. Brain Res. 2010. Vol. 208. № 2. P. 626-635.

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