The effect of thyroid hormones on the action of some centrally acting drugs

Abstract

Summary1. The effect of administration of thyroxine or thyroidectomy on the pharmacological action of (+)-amphetamine, caffeine, hexobarbitone and morphine was determined in rats or mice. 2. Locomotor activity induced by (+)-amphetamine or caffeine was increased by hyperthyroidism and decreased by hypothyroidism.3. The LD50s of (+)-amphetamine and caffeine in hyperthyroid rats were 1/30 and 2/5 that of control rats. With each drug, the LD50 regression lines in hyperthyroid and control rats were not parallel, suggesting that hyperthyroidism modifies the mechanism of the toxic effects. Hypothyroidism reduced toxicity to (+)-amphetamine. 4. Hexobarbitone sleeping time was prolonged in hyperthyroid male rats, but was shortened in hyperthyroid female rats. In control rats, sleeping time was approximately four times as long in females as it was in males. Ethinyloestradiol treatment and castration also prolonged sleeping time in male rats. No further prolongation was produced by combined administration of thyroxine and ethinyloestradiol, but thyroxine further prolonged the sleeping time of castrated rats indicating that its mode of action in producing these changes is not mediated via sex hormones. 5. In contrast to rats, a sex difference in the duration of action of hexobarbitone was not found in mice. Thyroxine prolonged sleeping time equally in each sex.

Thyroid hormones in the treatment of affective disorders

“…This synergism was since then reported in the cardiovascular (98) and gastrointestinal systems (99) and in adipose tissues (100). psychoactive drugs (50). In addition, hyperthyroid animals were found to be particularly vulnerable to the toxic effects of drugs enhancing catecholamine activity, e.g.…”

“…In addition, hyperthyroid animals were found to be particularly vulnerable to the toxic effects of drugs enhancing catecholamine activity, e.g. psychoactive drugs (50).…”

Potentiation of amphetamine-induced hyperactivity in the adult mouse following neonatal thyroxine administration

“…The effects of neonatal hyperthyroidism appear similar, although not identical, to those of hyperthyroidism induced in the adult. Adult hyperthyroid mice show increased activity following amphetamine injections, but the temporal pattern of locomotor response remains unaltered (Askew, 1962;Coville & Telford, 1970).…”

“…Catecholamine systems were studied because thyroxine-CA interactions have previously been reported in both the infant and adult rat. The hyperthyroid state in the adult yields increased CA activity and increased CA receptor sensitivity (ErnIen, Segal, & Mandell, 1972;Engstrom, Svensson, & Waldeck, 1974;Ito , Valcana, & Timiras, 1977) , as well as increased behavioral response to and toxicity of the CA stimulant amphetamine (Askew, 1962;Coville & Telford , 1970;Halpern, Drudi-Baracco, & Bessirard, 1964). Some of these effects have also been reported after neonatal hyperthyroidism (Rastogi & Singhal, 1976).…”

The role of microsomal oxidation in the regulation of monoamine oxidase activity in the brain and liver of rats

“…We have studied the relationship between microsomal oxidation, as indexed by hexobarbital sleep time (HST) (Coville and Telford 1970;Pappas et al 1993;Cherala et al 2007), and MAO activity in brain and liver. Sleep was induced by the hexobarbital, which is barbiturate derivative (Pappas et al 1993;Lewis et al 1997).…”