Low dose nicotine administration improves attentional performance in rats but is not blocked by nicotinic antagonists

Nicotine has been found by a variety of studies to improve cognitive function, including attention in both humans and experimental animals. However, it is not known which nicotinic acetylcholine receptor (nAChR) stimulating vs. desensitizing effects of nicotine are responsible for the cognitive improvement. Young adult female Sprague-Dawley rats were trained on an operant visual signal detection task to assess sustained attention. Then, they were administered nicotine subcutaneously (sc) in low doses of 0, 0.01, 0.02 or 0.04 mg/kg (N = 10-11/group), 20 min before the test sessions. In the next phase, nicotine or vehicle saline was given alone or in combination with doses of 4 and 8 mg/kg (sc) of dihydro-β-erythroidine (DHβE), an α4β2 nicotinic receptor antagonist or methyllycaconitine (MLA), an α7 nicotinic receptor antagonist, to determine whether any effects caused by nicotine would be blocked by co-administration of these nAChR antagonists. Our results show that both 0.01 mg/kg and 0.04 mg/kg nicotine doses caused modest, but significant improvement in percent correct on the attentional test relative to control rats, while the 0.02 mg/kg nicotine dose had a marginal (p < 0.10) improvement that did not reach statistical significance. The significant improvement in percent correct performance on the attention test continued to be evident during the second phase of the study in which nAChR antagonists were co-administered. The rats given 0.01 mg/kg of nicotine continued to show a significant improvement in percent correct relative to the saline vehicle even in the face of the higher dose of each nicotinic antagonist. Our results show that low dose nicotine-induced attentional performance was not reversed by specific nAChR antagonists such as DHβE and MLA. This is consistent with the hypothesis that the nAChR desensitizing effect of nicotine, with low dose of nicotine, rather than the receptor stimulatory effect of nicotine underlies its action of improving attentional performance.