Аннотация:
The orexin family of hypothalamic neuropeptides was shown to participate in reinforcement mechanisms relevant to both food and drug reward. In the paper, the role of orexin A receptors (OX1R) of the bed nucleus of stria terminalis (BNST) in reinforcement mechanisms and dependence from psychostimulants like amphetamine was studied in rats. The adult male Wistar rats were implanted with stimulating electrodes to the lateral hypothalamus. Simultaneously, the microcanules were implanted into the BNST to inject the OX1R antagonist SB-408124. SB-408124 (Sigma, USA) was dissolved in distilled water and injected into the BNST (1 g/1 l in volume for each injection within 1 minute) or intraventricularly (iv) 5 µg/5 l for 1 minute. The rats were trained to perform intracranial self-stimulation in the Skinner box using fixed ratio regimen, and then the effects of the OX1R selective antagonist SB-408124 on brain stimulation-reward (BSR) were measured as changing of BSR threshold and BSR frequency. In our experiments, amphetamine (1 mg/kg ip) enhanced the BSR frequency by 32% and reduced BSR threshold by 28% demonstrating a typical stimulating effect. SB-408124 injected iv or into the BNST had no effect on self-stimulation of the lateral hypothalamus. SB-408124 administered into the BNST attenuated amphetamine self-stimulation from +32% till +5% and reduction of BSR threshold from 18% till 12%. SB-408124 injected iv 2-fold decreased self-stimulation indexes activated with amphetamine. BNST is one of the extended amygdala system structures, regulating emotional behavior. If we block OX1R in the BNST we can reduce reinforcing properties of narcogenics of psychostimulant type that is very important in searching drugs to prevent psychostimulants abuse.
Ключевые слова:
bed nucleus of stria terminalis, self-stimulation, extended amygdala, reinforcement, orexin A, orexin antagonists, SB-408124