Antagonism of the anxiolytic effect of nicotine in the dorsal raphe nucleus by dihydro-beta-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 raphé 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 (DH beta E) 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 DH beta E. DH beta E (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 DH beta E, our results suggest that the anxiolytic effect of nicotine in the DRN is mediated by the alpha 4 beta 2 nicotinic receptor subtype.