Pharmacological comparison of the rat and guinea-pig cortical high affinity 5-hydroxytryptamine uptake system

The pharmacological characteristics of the high affinity [3H]5-hydroxytryptamine ([3H]5-HT) uptake system were investigated in the cerebral cortex of the rat and guinea-pig. In crude cortical synaptosomal preparations from the rat and guinea-pig, [3H]5-HT accumulated with high affinity (Km, 72 +/- 12 and 57 +/- 14 nM for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5) and with a comparable maximum activity (Vmax, 1.22 +/- 0.21 and 0.90 +/- 0.19 pmol/min/mg protein for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5). Competition studies employing a range of structurally diverse competing compounds showed that the [3H]5-HT uptake was pharmacologically similar in both preparations. However, citalopram possessed approximately 10-fold weaker affinity to prevent [3H]5-HT uptake in the guinea-pig preparation when compared to the rat and all of the tricyclic antidepressants assessed in the present studies (amitriptyline, nortriptyline, desipramine and imipramine) displayed higher affinity in the guinea-pig preparation when compared to the rat. It is concluded that the high affinity 5-HT uptake systems in the rat and guinea-pig cortex are similar but may not be identical.