NEUROCHEMICAL MECHANISMS OF THE NUCLEUS ACCUMBENS REALIZING THE REINFORCING EFFECTS OF SELF-STIMULATION OF THE LATERAL HYPOTHALAMUS



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Abstract

The purpose of the investigation was to clear the significance of GABA, dopamine and corticoliberin (CRF) systems of the nucleus accumbens 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 nucleus accumbens to inject the drugs studied (1 |!g in 1 |ll in volume for each injection). Some drugs, lidocain, a blocker of sodium influx ionic currents, antagonists of GABAa receptors bicuculline, D 1 dopamine receptors SCH23390, D 2 dopamine receptors sulpiride and CRF receptors astessin, which were administered intrastructurally into the nucleus accumbens, were used for pharmacological analysis. Bicuculline > astressin > sulpiride > SCH23390 (the drugs are located in the range of descending inhibition activity), administered into the nucleus accumbens, inhibited, but lidocain, a blocker of sodium influx ionic currents, enhanced self-stimulation of the lateral hypothalamus. The reinforcing properties of all psychoactive drugs (amphetamine, fentanyl, sodium ethaminal and leu-enkephaline) were changed on the background of their action. After administration of sulpiride amphetamine had no effect, and after bicuculline, lidocaine and SCH23390 the amphetamine effect, clear reproducible from the lateral hypothalamus, was decreased. Ch the other hand, both bicuculline and sulpiride did not pre- vent of psychoactivating effect of opioid analgetic fentanyl. In all other cases the positive effect of fentanyl inverted into negative one (lidocain, SCH23390, astressin). The blockade of dopamine receptors (SCH23390, sulpiride) and CRF receptors (CRF) did not change sodium ethaminal effect whereas bicuculline and lidocaine declined them. None blocker instead of astressin changed the inhibitory effects of leu-enkephaline on hypothalamic self-stimulation significantly. In the latter case, astressin strengthened the negative action of leuenkephaline on self-stimulation. It is concluded that the nucleus accumbens controls the hypothalamic self-stimulation via GABA- and CRF-ergic mechanisms preferably, which are able to limit the positive effects of narcogenic drugs.

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About the authors

P D Shabanov

Anichkov Department of NeuroPharmacology, Institute of Experimental Medicine

Email: pdshabanov@mail.ru
St.-Petersburg, Russia

A A Lebedev

Anichkov Department of NeuroPharmacology, Institute of Experimental Medicine

St.-Petersburg, Russia

References

  1. Шабанов П. Д. Психофармакология.- СПб.: Н-Л, 2008. - 384 с.
  2. Шабанов П. Д., Сапронов Н. С. Психонейроэндокринология.- СПб.: Информ-Навигатор, 2010.- 984 с.
  3. Carlezon W.A., Thomas M. J. Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis // Neuropharmacology.-2009.- Vol. 56, Suppl. 1.- P. 122-132.
  4. Koob G. F. Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory // Pharmacopsychiatry.- 2009.- Vol. 42, Suppl. 1.- P. S32-S41.
  5. Meredith G. E. The synaptic framework for chemical signaling in nucleus accumbens // Ann. NY Acad. Sci.- 1999.- Vol. 877.- P. 140-156.
  6. Kelley A. E. Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning // Neurosci. Biobehav. Rev.- 2004.- Vol. 27.- P. 765-776.
  7. 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.
  8. Surmeier D. J., Ding J., Day M., Wang Z., Shen W. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons // Trends Neurosci.- 2007.- Vol. 30.- P. 228-235.
  9. Шабанов П. Д., Лебедев А. А. 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.
  10. Alheid G. F., Heimer L. Theories of basal forebrain organization and the «emotional motor system» // Progr. Brain Res.- 1996.- Vol. 107.-P. 461-484.
  11. 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.
  12. Bruijnzeel A. W., Gold M. S. The role of corticotrophin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence // Brain Res. Rev.- 2005.- Vol. 49.- P. 505-528.
  13. Sarnyai Z., Shaham Y., Heinrichs S. C. The role of corticotropin-releasing factor in drug addiction // Pharmacol. Rev.- 2001.- Vol. 53.-P. 209-243.
  14. Ko.nig K. P., KlippelA. A. A stereotaxic atlas of the forebrain and lower parts of the brain stem.- Baltimore, 1963.- 214 p.
  15. Лебедев А. А., 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.
  16. Шабанов П. Д., Лебедев А. А., Мещеров Ш. К. Дофамин и подкрепляющие системы мозга.- СПб.: Лань, 2002.- 208 с.
  17. Шабанов П. Д., Лебедев А. А., Стрельцов В. Ф. Гормональные механизмы подкрепления.- СПб.: Н-Л, 2008.- 208 с.
  18. 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.
  19. Waraczynski M. Lidocaine inactivation demonstrates a stronger role for central versus medial extended amygdala in medial forebrain bundle selfstimulation // Behav. Brain Res.- 2006.- Vol. 173, № 2.- P. 288-298.
  20. Waraczynski M. GABA receptor agonism in the sublenticular 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.
  21. 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.
  22. 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.
  23. Koob G. F. Neurobiological substrates for the dark side of compulsivity in addiction // Neuropharmacology.- 2009.- Vbl. 56, Suppl. 1.- P. 18-31.

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