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Expression and function of 5HT-1A receptor in brains of Wistar-Zagreb 5HT rats

Introduction. By selective breeding for the extreme values of platelet serotonin level and platelet serotonin uptake, two sublines of rats with constitutionally upregulated/downregulated platelet serotonin transporter (5HTt) have been developed (Wistar-Zagreb 5HT rats). In previous studies, these sublines demonstrated significant differences in the expression of platelet 5HTt at the level of both mRNA and protein. Study on 5HTt gene expression in brains did not show significant differences between the sublines, although neuropharmacological and behavioral studies indicated that changes in central 5HT homeostasis might be expected. Here, we searched for possible adaptive/compensatory changes in expression and/or function of cortical 5HT-1A receptors of Wistar-Zagreb 5HT rats, since 5HT-1A receptors are, besides 5HTt, the most important regulators of serotonergic neurotransmission. Materials & Methods. Studies were performed on animals from the 15th breeding generation. Semi-quantitative RT-PCR was performed on RNA isolated from frontal cortex, using two housekeeping genes,  -actin and cyclophylin B, as a reference. Functional analysis of cortical 5HT-1A receptors was performed by radioligand binding method, using [3H]-8-hydroxy-2-(di-N-propylamino)tetraline (8-OH-DPAT) as the radioactive ligand. Results. There were no difference in mRNA expression of cortical 5HT-1A receptors between the sublines of Wistar-Zagreb 5HT rats. At the functional level, the sublines did not differ, either in number of cortical 5HT-1A binding sites (Bmax) or in the receptor affinity for ligand (Kd). Conclusion. Constitutional alteration in serotonergic neurotransmission of Wistar-Zagreb 5HT rat sublines, induced by up/downregulation of serotonin transporter, did not result in change in expression or function of cortical 5HT-1A receptors in physiological conditions. Further studies will be aimed to the 5HT (5HT-1A, as well as the other) receptor expression and/or function after specific pharmacological challenge, when possible subtle differences between sublines could become more detectable.

5HT-1A receptor; expression; function; Wistar-Zagreb 5HT rat

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