A. Kulikov et al., Effects of experimental hypothyroidism on 5-HT1A, 5-HT2A receptors, 5-HT uptake sites and tryptophan hydroxylase activity in mature rat brain, NEUROENDOCR, 69(6), 1999, pp. 453-459
The study was aimed at investigating the repercussions of deficiency in thy
roid function with and without thyroid hormone (TH) replacement on the neur
ochemical entities which underly serotonin (5-HT) neutrotransmission, namel
y 5-HT1A, 5-HT2A receptors, 5-HT transporter and tryptophan hydroxylase (TP
H) in the mature brain. Surgically thyroidectomized male Wistar rats receiv
ed: (1) an iodine-free diet to produce severe hypothyroidism; (2) hormonal
replacement with 15 mu g/kg/day of thyroxine (T4) for 21 days to normalize
serum TH levels, or (3) hormonal replacement with 200 mu g/kg/day of T4 for
14 days to produce an excess of circulating THs. Sham-operated rats were u
sed as controls. Neither hypothyroidism nor an excess in serum TH levels af
fected H-3-8-OH-DPAT binding to 5-HT1A receptors, H-3-citalopram binding to
5-HT transporter and TPH activity in various brain structures indicating t
hat, in the mature brain, the presynaptic entities of 5-HT neurotransmissio
n are resistant to large variations in TH levels. By contrast, hypothyroid
rats had a significant decrease in B-max of H-3-ketanserin binding to corti
cal 5-HT2A receptors compared to controls. Cortical 3H-ketanserin binding i
n thyroidectomized rats was normalized after replacement with low-dose T4.
Excess serum TH levels in thyroidectomized rats did not produce a ny change
s in cortical 5-HT2A receptors when compared to thyroidectomized rats with
normalized TH levels. The present data suggest that the decrease in cortica
l 5-HT2A receptors is the main neurochemical event underlying the impairing
effect of hypothyroidism on 5-HT neurotransmission.