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

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.