The effect of p-chloroamphetamine and p-chlorophenylalanine on the level of thyrotropin-releasing hormone and its receptors in some brain structures and lumbar spinal cord of the rat

Abstract

The concentration of thyrotropin-releasing hormone (TRH) and the density and affinity of TRH receptors were examined in the ventral and dorsal lumbar spinal cord, nucleus accumbens and striatum of rats with the 5-hydroxytryptamine (5-HT) nerve terminal destroyed with p-chloroamphetamine (PCA), or in animals treated with the inhibitor of 5-HT synthesis p-chlorophenylalanine (PCPA). PCA (2 × 10 mg/kg i.p., 9 and 8 d before killing) and PCPA (3 × 300 mg/kg i.p., 72, 48 and 24 h before killing)—either of them dramatically diminishing the 5-HT and 5-HIAA concentrations in all the examined structures—reduced the TRH level and increased the density of TRH receptors in the ventral lumbar spinal cord. PCPA also reduced the TRH content in the nucleus accumbens. The PCA-induced reduction in the TRH level and increase in the density of TRH receptors in the ventral lumbar spinal cord were significantly attenuated by citalopram (2 × 20 mg/kg i.p., 30 min before PCA), a selective inhibitor of 5-HT uptake. Our results constitute a further proof that coexistence of TRH and 5-HT takes place in the ventral lumbar spinal cord and then indicate that other form(s) of relationship between 5-HT and TRH may exist in some parts of the central nervous system. They also suggest that an up-regulation of TRH receptors occurs in the spinal cord as a result of TRH depletion.