The effect of fenfluramine on the thyrotropin-releasing hormone (TRH) content in the rat brain structures and lumbar spinal cord

Abstract

The effect of fenfluramine (20 mg/kg i.p.) was studied on the thyrotropin-releasing hormone (TRH) content in several brain structures and the ventral part of the lumbar spinal cord of the rat. The effect of fenfluramine on the concentration of 5-hydroxytryptamine (5-HT) in some brain structures and the lumbar spinal cord was also examined. It was found that fenfluramine had no effect on the TRH level in the hypothalamus, hippocampus, occipital cortex, septum, nucleus accumbens and ventral part of the lumbar spinal cord, though the drug produced a profound depletion (by more than 60%) of 5-HT in the hypothalamus, nucleus accumbens, striatum and lumbar spinal cord. On the other hand, fenfluramine significantly increased the TRH content in the striatum, this effect was completely abolished by citalopram (20 mg/kg i.p.) or metergoline (10 mg/kg i.p.) Citalopram also prevented the fenfluramine-induced depletion of the striatal 5-HT. These results indicate a separate neuronal storage of TRH and 5-HT in the structures (ventral part of the lumbar spinal cord, nucleus accumbens, septum) in which the peptide and indoleamine coexist in 5-HT neurons. They also suggest that the fenfluramine-induced increase in the striatal TRH concentration is due to 5-HT release and stimulation of 5-HT receptors.