Effects of venlafaxine given repeatedly on α 1 ‐adrenergic, dopaminergic and serotonergic receptors in rat brain

Venlafaxine (VEN), a representative of a new class of antidepressants (serotonin and noradrenaline reuptake inhibitors, SNRI), administered repeatedly affects—as was demonstrated by us previously—the behavioural responsiveness of α 1 ‐adrenergic, dopaminergic (D 2 and D 3 ) and serotonergic systems to their agonists. In the present study we aimed to find out whether parallel changes in the binding to the respective receptors also occurred. The experiment was carried out on male Wistar rats. VEN was administered in a dose of 10 mg/kg once or repeatedly (14 days, twice daily). The obtained results showed that VEN did not change the binding ( B max and K D ) of α 1 ‐adrenergic receptors to [ 3 H]‐prazosin in the cerebral cortex, having increased only its displacement by phenylephrine. The binding ( B max and K D ) to D 1 and D 2 receptors in the limbic forebrain and the striatum was not affected by repeated venlafaxine when [ 3 H];‐SCH 23390 and [ 3 H]‐spiperone, respectively, were used as ligands. When [ 3 H]‐quinpirole was used as a ligand, the binding was enhanced in the striatum, the nucleus accumbens (shell and core) and islands of Calleja. VEN also increased the binding of [ 3 H]‐7‐OH‐DPAT to D 3 receptors in islands of Calleja and the nucleus accumbens (shell). In the serotonergic system, a decrease in the density of 5‐HT 1A receptors was observed in the hippocampus, whereas no changes occurred in the binding of 5‐HT 2 receptors in the cortex. Thus VEN given repeatedly enhanced the binding (of the ligands that are agonists) to dopamine D 2 and D 3 receptors. Weaker effects were observed in the α 1 ‐adrenergic and the serotonergic systems. Copyright © 1999 John Wiley & Sons, Ltd.