H1, H2, and H3 receptors contribute to drinking elicited by exogenous histamine and eating in rats

Roles for H1, H2, and H3 receptor subtypes for drinking elicited by exogenous histamine and drinking elicited by eating was examined in adult male Sprague-Dawley rats. Drinking elicited by SC 5 mg/kg histamine was: (a) inhibited approximately 30% by H1 antagonism using IP 1 mg/kg dexbrompheniramine (DXB); (b) inhibited approximately 30% by H2 antagonism using IP 16 mg/kg cimetidine (C); (c) inhibited approximately 40% by H3 antagonism using SC 10 mg/kg thioperamide (Th); (d) inhibited approximately 80% by combined H1 and H2 antagonism using IP DXB plus IP C; (e) inhibited approximately 85% by combined H1 and H3 antagonism using IP DXB plus SC Th; (f) inhibited approximately 70% by combined H2 and H3 antagonism using IP C plus SC Th; and (g) abolished by combined H1, H2, and H3 antagonism using IP DXB plus IP C plus SC Th. For rats eating pellets and drinking after 24-h food deprivation: (a) systemic injections of DXB, C, and Th, sufficient to abolish drinking elicited by SC histamine, inhibited water/food ratio (W/F) by approximately 20%; (b) ICV injections (through a chronic cannula in a lateral ventricle) of 50 micrograms DXB plus 100 micrograms C plus 60 micrograms Th inhibited W/F by approximately 20%. For rats drinking after IG infusion (through a chronic gastric catheter) of 2 ml 1,800 mOsm/kg NaCl: (a) systemic injections of DXB, C, and Th, sufficient to abolish drinking elicited by SC histamine, inhibited water intake by approximately 70%; (b) IP DXB alone and IP C alone failed to inhibit water intake; (c) IP Th alone inhibited water intake by approximately 20%; (d) IP DXB combined with IP C inhibited water intake by approximately 55%. The results demonstrate the involvement of H1, H2, and H3 receptors for drinking elicited by exogenous histamine, and our findings extend the evidence for a role for endogenous histamine and H1, H2, and H3 receptor subtypes for drinking elicited by eating, including drinking elicited by gastrointestinal osmotic consequences of eating that can increase systemic plasma osmolality.