H-2 HISTAMINERGIC CONTROL OF INHIBITION OF EATING INDUCED BY INTRAGASTRIC NACL IN RATS

A role for endogenous histamine and histamine receptor subtypes in med iating the inhibition of eating induced by intragastric (i.g.) hyperto nic NaCl was examined in adult male Sprague-Dawley rats surgically equ ipped with a chronic gastric catheter. The i.g. infusion of 2 mt 900 o r 1,800 mOsm/kg of NaCl inhibited: 1) ingestion of pellets in rats eat ing after 24-h food deprivation; and 2) ingestion of cookies in rats e ating without prior deprivation. The H-1 receptor antagonists dexbromp heniramine (DXB; 1 mg/kg) and pyrilamine (PYR; 4 mg/kg) did not attenu ate the inhibitory effects of i.g. 900 or 1,800 mOsm/kg of NaCl for ra ts eating pellets and for rats eating cookies. The H-2 antagonists cim etidine (CIM; 16 mg/kg) and metiamide (MET; 16 mg/kg) attenuated the i nhibitory effects of i.g. 1,800 mOsm/kg of NaCl upon ingestion of cook ies, but intracerebroventricular (i.c.v.) infusion (through a chronic indwelling cannula) of 100 mu g of CIM did not mimic this effect of in traperitoneal (i.p.) CIM. The i.p. CIM failed to attenuate the inhibit ion of eating cookies produced by i.p. octapeptide of cholecystokinin (CCK-8; 3 mu g/kg). The H-3 antagonist thioperamide (TH; 10 mg/kg i.p. ) and the H-3 agonist R-alpha-methylhistamine (RAM; 3 mg/kg i.p.) did not alter the inhibitory effect of i.g. 1,800 mOsm/kg of NaCl for rats eating cookies. Combined treatments of systemic DXB plus CIM, and DXB plus CIM plus thioperamide (TH) did not reverse the inhibitory effect s of i.g. 1,800 mOsm/kg of NaCl upon ingestion of cookies. Finally, i. p. DXB, but not CIM, attenuated the ability of i.g. 900 mOsm/kg of NaC l to increase water intake; conversely, i.p. CIM, but not DXB, attenua ted the ability of i.g. 900 mOsm/kg of NaCl to inhibit eating of cooki es. These findings demonstrate a double dissociation of effects upon i ngestive behavior: H-1, but not H-2, antagonism attenuates the effect of i.g. hypertonic NaCl on water intake, whereas ii,, but not ii,, ant agonism attenuates the inhibition of eating produced by i.g. hypertoni c NaCl. These results demonstrate that different subtypes of periphera l and/or central histamine receptors contribute to different behaviora l consequences of postprandial gastrointestinal osmotic loads in rats. (C) 1998 Elsevier Science Inc.