Impact of moderate prenatal alcohol exposure on histaminergic neurons, histidine decarboxylase levels and histamine H receptors in adult rat offspring.

We have reported that moderate prenatal alcohol exposure (PAE) elevates histamine H receptor-mediated inhibition of glutamatergic neurotransmission in dentate gyrus (DG), and that the H receptor antagonist ABT-239 ameliorates PAE-induced deficits in DG long-term potentiation. Here, we investigated whether PAE alters other markers of histaminergic neurotransmission. Long-Evans rat dams voluntarily consumed either a 0% or a 5% ethanol solution 4 h each day throughout gestation. Young adult female offspring from each prenatal treatment group were used in histidine decarboxylase (HDC) immunohistochemical studies of histamine neuron number in ventral hypothalamus, quantitative Western blotting studies of HDC expression in multiple brain regions, radiohistochemical studies of H receptor density in multiple brain regions, and in biochemical studies of H receptor-effector coupling in dentate gyrus. Rat dams consumed a mean of 1.90 g of ethanol/kg/day during pregnancy. This level of consumption did not affect maternal weight gain, offspring birth weight, or litter size. PAE did not affect the number of HDC-positive neurons in ventral hypothalamus. However, HDC expression was reduced in frontal cortex, dentate gyrus, and cerebellum of PAE rats compared to controls. Specific [I]-iodoaminopotentidine binding to H receptors was not altered in any of the brain regions measured, nor was basal or H receptor agonist-stimulated cAMP accumulation in DG altered in PAE rats compared to controls. These results suggest that not all markers of histaminergic neurotransmission are altered by PAE. However, the observation that HDC levels were reduced in the same brain regions where elevated H receptor-effector coupling was observed previously raises the question of whether a cause-effect relationship exists between HDC expression and H receptor function in affected brain regions of PAE rats. This relationship, along with the question of why these effects occur in some, but not all brain regions, requires more-detailed investigation.