How can the acceleration effects of thyroid hormones be explained? Studies examining the relationship between thyroid hormones and neurotransmitter systems have focused on the noradrenergic and serotonin systems. In studies assessing the thyroid-serotonin systems, the effects of thyroid hormone application to experimentally induced hypothyroid or euthyroid animals include an increase in cortical 5-HT concentrations and a desensitization of autoinhibitory 5-HT
1A receptors in the raphe area, resulting in disinhibition of cortical and hippocampal 5-HT release
+(43,
+44). A recent in vivo microdialysis study by Gur et al.
+(45) indicated a loss of autoinhibitory 5-HT
1A receptor sensitivity mediated by T
3. In the latter study, the decrease in hippocampal and cortical serotonin release, which should follow the application of a 5-HT
1A agonist, was significantly reduced in euthyroid rats by administration of T
3 or combined T
3 and clomipramine
+(45). These results indicate that thyroid hormone application may reduce autoinhibitory 5-HT
1A receptor activity and thus increase cortical serotonin release. In this way, it may have actions similar to those of pindolol, a 5-HT
1A receptor antagonist that when added to SSRI treatment facilitates serotonin release
+(3). Further evidence for an interaction between thyroid status and the serotonin system derives from studies that have demonstrated a significantly blunted cortisol and prolactin response to the 5-HT agonist
d-fenfluramine in hypothyroid patients
+(46,
+47). This blunted response to
d-fenfluramine stimulation normalized with thyroid hormone replacement therapy, suggesting reduced central 5-HT functioning in hypothyroidism
+(47). Thyroid hormones also appear to play an important role in regulating central noradrenergic function, and its impact on this system may also contribute to the acceleration effect. Recent findings indicate that T
3 may function as a cotransmitter with norepinephrine in the adrenergic nervous system
+(48).