Antagonism of the anxiolytic effect of nicotine in the dorsal raphe nucleus by dihydro-β-erythroidine

Nicotine has been reported to reduce anxiety in humans and in a number of animal tests. In the social interaction test of anxiety, administration of low doses of nicotine into the dorsal raphe nucleus (DRN) increases the time spent in social interaction without producing accompanying changes in locomotor activity, suggesting that nicotine acts specifically to reduce anxiety in this brain region. The present study examined the ability of the high-affinity competitive nicotinic receptor antagonist dihydro-beta-erythroidine hydrobromide (DHbetaE) to antagonise the anxiolytic effect of nicotine following intra-DRN infusion using the social interaction test. The increase in social interaction observed after administration of nicotine (5 ng) into the DRN was completely reversed by coadministration of 100 ng DHbetaE. DHbetaE (100 ng), when administered alone into the DRN, did not modify the time spent in social interaction. However, it did significantly increase locomotor activity, and this effect was not antagonised by coadministration of nicotine (5 ng) into the DRN. Because of the pharmacological profile of DHOE, our results suggest that the anxiolytic effect of nicotine in the DRN is mediated by the alpha4beta2 nicotinic receptor subtype. (C) 2001 Elsevier Science Inc. All rights reserved.