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The aim of investigation was to study the role of the hypothalamic serotoninergic system in mechanisms of blocking action of the orexin receptor antagonist on amphetamine-induced self-stimulation in rats. Methods . 27 male Wistar rats weighing 250-300 g were the object of the investigation. One week before the experiment, the microelectrodes were implanted into the lateral hypothalamus for self-stimulation and microcannulas into the bad nucleus of stria terminalis (BNST) for microinjections. The electrodes were implanted bilaterally and cannulas unilaterally (right or left). Intact rats and rats treated with amphetamine were controls. On the day of the experiment, amphetamine 1 mg/kg i.p. was injected, and then SB-408124 1 µg in 1 µl was administered into the BNST in 10 min. The rats were decapitated in 15 min after microinjection of SB-408124. The level of serotonin (Ser) and its metabolite 5-HIAA was determined in the right and the left hypothalamus by HPLC with electrochemical detection. Results . In intact rats, the 5-HIAA level in the left hypothalamus was higher than in the right one (p < 0.05). After systemic administration of amphetamine the ratio of 5-HIAA/Ser was significantly decreased both in the left (p < 0.05) and the right (p < 0.05) hypothalamus. The levels of Ser and 5-HIAA stated symmetrical. It is important that effects of orexin antagonist after amphetamine administration appeared only on the side contralateral to microinjection being significantly only in the left hypothalamus. After administration of orexin antagonist into the right BNST, the level of Ser in the left hypothalamus increased compared both to intact rats (p < 0.05) and rats treated with amphetamine (p < 0.05). Conclusion . The results suggest that the left hypothalamus plays a leading role in developing of self-stimulation reaction and support the hypothesis that the serotoninergic system is involved in mechanism of blocking action of orexin receptors antagonist on self-stimulation activated with amphetamine.

Blockade of orexin receptors in the bed nucleus of stria terminalis increases serotonin level only in the left hypothalamus