The effects of hyperthyroidism or hypothyroidism, alone or in combination with the tricyclic antidepressant desmethylimipramine (DMI), on brain beta-adrenergic and serotonin (5HT2) receptors were studied in adult male Sprague-Dawley rats. Intraperitoneal administration of T3 or T4 for 7 days increased the number of cortical beta-adrenergic and 5HT2 receptors. These increases were significant at levels of 250 micrograms/kg or above for both hormones. Neither thyroidectomy nor "reverse" T3 (rT3) (500 micrograms/kg) produced an effect on either receptor type. The down-regulation of beta-adrenergic receptors produced by daily subcutaneous injections of 20 mg/kg of DMI for 7 days was partially offset by concurrent administration of T4, whereas the down-regulation of 5HT2 receptors produced by the drug was not affected by concurrent administration of either T3 or T4. Hypothyroidism (thyroidectomy) did not significantly affect the adaptation of these receptor populations to DMI. As regards brain regions other than cortex, T4 (250 micrograms/kg) produced the same changes in hippocampus as in cortex, while thyroidectomy decreased beta-adrenergic receptors only in the cerebellum. Thyroxine also elevated 5HT2 receptors in the hippocampus; thyroidectomy caused a significant decrease in 5HT2 receptors in the striatum.

Studies of the effects of thyroid hormones on the uptake of neurotransmitters by homogenates of rat cerebral cortex have revealed a significant competitive inhibition of neuronal uptake of [3H]GABA by thyroid hormones (T3 greater than T4 greater than rT3). The IC50 for inhibition of GABA uptake by T3 was estimated at 4 microM and that of T4 at 11 microns. GABA uptake in homogenates of cerebral cortex from hypothyroid rats was significantly enhanced over that of controls; however, uptake in tissues from hyperthyroid rats was not significantly diminished.