HISTAMINERGIC CONTRIBUTION TO THE METABOLIC EFFECTS OF NEUROGLUCOPENIA

We examined the contribution of central histamine receptor (H-1 and H- 2) blockade to the glucoregulatory responses to intracerebroventricula r 2-deoxy-D-glucose (2-DG) in conscious dogs. Intracerebroventricular 2-DG (2.5 mg . kg(-1) . min(-1) for 15 min) increased plasma glucose ( 2-fold), blood lactate (4-fold), and glycerol (2-fold) levels. The rat e of hepatic glucose production (R-a), determined isotopically, was in creased two-fold. Significant increases over basal were also noted in plasma epinephrine, norepinephrine, insulin, glucagon, and cortisol. P retreatment with cyproheptadine and cimetidine (100 mu g each icv 15 m in before 2-DG) attenuated the 2-DG-induced hyperglycemia by similar t o 50% and delayed and attenuated the increase in glucose R-a (similar to 85% vs. 2-fold in group 1). Pretreatment with H-1 and H-2 antagonis ts inhibited the increases in epinephrine, norepinephrine, and glucago n in response to neuroglucopenia but did not affect the cortisol respo nse. These findings suggest that some of the metabolic effects of neur oglucopenia, particularly the hyperglycemic response, the increased he patic uptake of gluconeogenic precursors, and the enhanced glucose R-a , are partly mediated through central histaminergic receptor activatio n. This appears to be through effects of histaminergic activation on t he autonomic and hormonal responses to central neuroglucopenia.