Histamine and serotonin independently elicit drinking in the rat

Drinking elicited by SC histamine or serotonin (5-HT) was studied in Sprague-Dawley male rats following 0.9% NaCl or combined antagonism of H1 and H2 histamine receptors using dexbrompheniramine (DXB) and cimetidine (C), or following antagonism of 5-HT receptors using methysergide (M). Histaminergic antagonism using IP 1 mg/kg DXB plus 16 mg/kg C abolished drinking elicited by SC 2.5 mg/kg histamine, but it failed to inhibit drinking elicited by the ED50 or by the ED100 for SC 5-HT in the same rats. Serotonergic antagonism using IP 3 mg/kg M abolished drinking elicited by SC 0.63 mg/kg 5-HT, but it failed to inhibit drinking elicited by the ED50 or by the ED100 for SC histamine in the same rats. These findings demonstrate that activation of peripheral 5-HT receptors is not necessary for SC histamine to elicit drinking and that activation of peripheral histamine receptors is not necessary for SC 5-HT to elicit drinking. This demonstrates that histamine and 5-HT activate different receptors to elicit drinking in the rat. The finding that the ED50 for histamine and the ED50 for 5-HT are not additive in their effects on drinking is consistent with the notion that a single mechanism mediates the dipsogenic effects of SC histamine and SC 5-HT in the rat.