Serotonergic regulation of the spinal cord content of thyrotropin releasing hormone in the cerebellar ataxia mutant mouse

Abstract

The effects of serotonin (5-HT) and various serotonin receptor antagonists on the spinal cord thyrotropin releasing hormone (TRH) content were studied in the rolling mouse Nagoya (RMN) and in the unaffected C3H mouse. TRH was extracted from the cervical, thoracic, lumbar, and sacral cord, at 1 h after the intraperitoneal injection of a serotonin precursor, 2 serotonin agonists, and 5 serotonin receptor antagonists. Administration of 5-hydroxytryptophan and 2-methyl-5-hydroxytryptamine resulted in an increase of the spinal cord TRH content in C3H mice, but not in RMN. Parachlorophenylalanine decreased the spinal cord TRH content in C3H mice, while it increased TRH levels in all regions of the RMN spinal cord. The TRH contents were decreased in all regions of the spinal cord after 5,7-dihydroxytryptamine administration in both C3H mice and RMN. In C3H mice, methysergide, mianserin, ketanserin, and spiperone significantly decreased the TRH content in all regions of the spinal cord, while 3α-tropanyl-1H-indole-3-carboxylic acid ester (ICS205–930) did not affect it. These antagonists paradoxically increased TRH levels in the cervical cord in RMN. The degradation of synthetic TRH by cord homogenates and the number and affinity of spinal cord serotonergic receptors (5-HT 1 and 5-HT 2) showed no significant difference between C3H mice and RMN. These results suggest that TRH turnover is abnormally regulated by serotonergic neurons in the RMN and that the dysfunction of the serotonergic nerves is attributable to the serotonin autoreceptor.