Involvement of Gaba- and Dopaminergic Mechanisms of the Bed Nucleus of the Stria Terminalis in the Reinforcing Effects of Psychotropic Substances Mediated via the Lateral Hypothalamus

Abstract

The aim of the present work was to identify the significance of the GABA and dopamine systems in the bed nucleus of the stria terminalis for the reinforcing effects of a number of psychoactive compounds (opiates, opioids, psychostimulants) on self-stimulation of lateral hypothalamus in rats. Bipolar electrodes were implanted into the lateral hypothalamus of male Wistar rats to study self-stimulation responses in a Skinner box; microcannulae were implanted into the bed nucleus of the stria terminalis (the extended amygdalar system) for administration of pharmacological agents (1 μg in 1 μl per injection). Analysis was performed using the influx Na+ ion current blocker lidocaine, the GABAA receptor antagonist bicuculline, the dopamine D1 receptor blocker SCH23390, and the dopamine D2 receptor blocker sulpiride, which were given directly into the bed nucleus of the stria terminalis. In order of decreasing activity, lidocaine > SCH23390 ≈ bicuculline suppressed the lateral hypothalamus self-stimulation reaction. The reinforcing effects of psychoactive substances (phenamine, fentanyl, sodium ethaminal, and leu-enkephalin) changed after administration of these agents. The results led to the conclusion that the bed nucleus of the stria terminalis has a controlling influence on the hypothalamus, this being predominantly GABAergic and dopaminergic in nature. GABA had a negative (inhibitory) effect. Dopamine, acting via D1 receptors, had a direct positive (activatory) effect on the lateral hypothalamus, while dopamine D2 receptors in the bed nucleus of the stria terminalis limited the positive effects of narcogens.