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.