Lesions of the neuronal histaminergic system or pharmacological blockade of @entity112 receptors, e.g., with @entity112 H1 receptor antagonists, can enhance the performance of @entity35 in several tests of learning and memory. The underlying neuronal systems that mediate these behavioral effects are not known. Here, we examined the effects of treatment with @entity112 H1 antagonists on extracellular levels of @entity934 ( @entity1617 ) in adult @entity35 anesthetized with @entity4774 (1.25 g/kg). @entity1617 was quantified using in vivo microdialysis and HPLC with electrochemical detection. Basal levels of @entity1617 in the frontal cortex and hippocampus were in the range of 0.54 +/- 0.13 and 0.96 +/- 0.17 pmol/20 min, respectively. Injection (intraperitoneally) of saline did not produce significant increases in @entity1617 levels, even though there was a slight and gradual increase in cortical @entity1617 levels throughout the course of the experiments (up to 4 h after an injection). Administration of the H1 receptor antagonist @entity17567 (intraperitoneally) produced a dose-dependent increase of cortical @entity1617 levels to a maximum of 260, 280, and 570% of baseline values after doses of 5, 10, and 20 mg/kg, respectively. In the hippocampus, @entity1617 content increased to a maximum of approximately 600% of baseline levels after @entity17567 administration (20 mg/kg, i.p.). Administration of the H1 antagonist @entity8765 (intraperitoneally) increased cortical @entity1617 content to a maximum of 300 and 500%, whereas hippocampal @entity1617 levels increased to 215 and 280% after doses of 10 and 20 mg/kg, respectively. In an additional experiment using nonanesthetized, freely moving @entity35 , cortical @entity1617 content showed a moderate increase (to 190%) after saline injections (intraperitoneally) and a much higher increase (to 370%) after @entity17567 treatment (20 mg/kg, i.p.). These data suggest that cortical and hippocampal levels of @entity1617 can be effectively modulated by systemic treatment with @entity112 H1 antagonists. The increases in @entity1617 levels produced by H1 antagonists may suggest that some histaminergic receptors exert an inhibitory influence over central @entity1617 levels. The enhanced availability of @entity1617 in the forebrain may contribute to the behavioral effects observed with H1 antagonist treatment.

@entity112 H1 receptor antagonists produce increases in extracellular XXXX in @entity35 frontal cortex and hippocampus.

@entity4774 :: ('MESH:D014520', 'Chemical') :: ['urethane'] @entity8765 :: ('MESH:D011738', 'Chemical') :: ['pyrilamine'] @entity1617 :: ('CHEBI:22614', 'Chemical') :: ['ACh'] @entity112 :: ('MESH:D006632', 'Chemical') :: ['histamine'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity17567 :: ('MESH:D002744', 'Chemical') :: ['chlorpheniramine'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity934 :: (MESH:D000109,Chemical) :: ['acetylcholine']
