Alterations in Serotonin Parameters in Brain of Thiamine‐Deficient Rats Are Evident Prior to the Appearance of Neurological Symptoms

Biochemical alterations of serotoninergic parameters have been demonstrated in experimental thiamine deficiency. In addition, hypophagia and hypothermia, two physiological processes associated with changes in the serotonin [5‐hydroxytryptamine (5‐HT)] system, are manifest early during the progression of thiamine deficiency. The binding of selected 5‐HT radioligands was therefore investigated in discrete brain regions of pyrithiamine‐induced thiamine‐deficient rats. Using quantitative receptor autoradiography, the binding of 8‐hydroxy‐2‐(di‐ n ‐[ 3 H]propylamino)tetralin, a ligand used to label the somatodendritic 5‐HT 1A autoreceptor of the dorsal raphe nucleus, was found to be unaffected in this region, suggesting that the structural integrity of the 5‐HT cell bodies is maintained throughout the course of pyrithiamine treatment. Increased binding of [ 3 H]‐ketanserin was observed in regions considered vulnerable as well as in some considered to be nonvulnerable during the course of thiamine deficiency. These binding changes, which appear to represent changes in the density of the postsynaptic 5‐HT 2A receptor population rather than the “tetrabenazine‐sensitive” vesicular monoamine transporter, are evident before the appearance of histopathologic lesions and coincide with altered tissue concentrations of 5‐HT. These data suggest that 5‐HT neurons, although structurally intact, are functionally affected early during the progression of thiamine deficiency. These alterations, which are likely a part of adaptive neuronal change consequent to thiamine dysfunction, may be important in the physiological manifestations and the learning deficits commonly encountered in experimental thiamine deficiency.