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Effects of neonatal dysthyroidism on serotonin type 1 and type 2 receptors in rat brain
Long-Evans, male and female rats born of mothers kept on an iodide-rich diet prior to delivery and during lactation, were fed this diet after weaning, thus becoming slightly hypothyroid. A more severe hypothyroidism was also provoked with the chronic administration of methimazole to Long-Evans iodide-supplemented, or Charles River iodine-deprived pups through the first month of age. Additional Long-Evans rats were made hyperthyroid with a daily injection of triiodothyronine (T3) through the first 29 days of age. Severe hypothyroidism in both strains of rats markedly increased the density of serotonin type 1 (5-HT1) and type 2 (5-HT2) receptors in the brain (less cerebellum, corpus striatum and olfactory bulbs) at 31-32 days of age. Receptor alterations were not correlated to either the rise in thyrotropin (TSH) levels in hypothyroidism or the direct influence of residual methimazole after the last treatment, or to neonatal malnutrition. This increase in 5-HT receptor density might represent an adaptive (supersensitivity) postsynaptic response to the state of central serotonergic hypofunction occurring in hypothyroidism. Though receptor alterations might be important, their precise functional role in the etiogenesis of hypothyroid-associated mental disturbances is difficult to ascertain.
Long-Evans, male and female rats born of mothers kept on an iodide-rich diet prior to delivery and during lactation, were fed this diet after weaning, thus becoming slightly hypothyroid. A more severe hypothyroidism was also provoked with the chronic administration of methimazole to Long-Evans iodide-supplemented, or Charles River iodine-deprived pups through the first month of age. Additional Long-Evans rats were made hyperthyroid with a daily injection of triiodothyronine (T3) through the first 29 days of age. Severe hypothyroidism in both strains of rats markedly increased the density of serotonin type 1 (5-HT1) and type 2 (5-HT2) receptors in the brain (less cerebellum, corpus striatum and olfactory bulbs) at 31-32 days of age. Receptor alterations were not correlated to either the rise in thyrotropin (TSH) levels in hypothyroidism or the direct influence of residual methimazole after the last treatment, or to neonatal malnutrition. This increase in 5-HT receptor density might represent an adaptive (supersensitivity) postsynaptic response to the state of central serotonergic hypofunction occurring in hypothyroidism. Though receptor alterations might be important, their precise functional role in the etiogenesis of hypothyroid-associated mental disturbances is difficult to ascertain.