The H1- and H2-histamine blockers chlorpheniramine and ranitidine applied to the nucleus basalis magnocellularis region modulate anxiety and reinforcement related processes

This study examined the effects of the H1-antagonist chlorpheniramine and the H2-antagonist ranitidine on reinforcement and anxiety-parameters following unilateral injection into the vicinity of the nucleus basalis magnocellularis (NBM). In Experiment 1, rats with chronically implanted cannulae were injected with chlorpheniramine or ranitidine (each at doses of 0.1, 1, 10 and 20 μg) and were placed into one of four restricted quadrants of a circular open field (closed corral) for a single conditioning trial. During the test for conditioned corral preference, when provided a choice between the four quadrants, only those rats injected with 10 or 20 μg chlorpheniramine spent more time in the treatment corral, indicative of a positively reinforcing action. None of the other doses of chlorpheniramine or of the H2-antagonist influenced rats' preference behavior. In Experiment 2, the elevated plus-maze (EPM) was used to gauge possible anxiolytic or anxiogenic effects of intra-basalis injection of chlorpheniramine or ranitidine (each at doses of 0.1, 1, 10 and 20 μg). A single injection of chlorpheniramine at 0.1 or 20 μg as well as ranitidine at 20 μg was found to exert anxiolytic-like effects in the EPM. Both compounds elevated the time spent on the open arms and increased scanning over the edge of an open arm. None of the other doses of the H1- and H2-antagonist influenced rats' behavior in the EPM. In sum, these findings show that H1- and H2-receptor antagonists differentially modulate reinforcement and fear-related processes in the NBM and thus, provide the first evidence for a behavioral relevance for the histaminergic innervation of this brain site.