The cholinergic system has been implicated in mediating attentional processes in humans and nonhuman animals.11,50,59,64,85,96 For example, in human studies, smoking a cigarette (e.g., nicotine administration) before presentation of a word list improved the number of words correctly recalled during a later test.83,96 Specifically, Warburton et al96 found that more words from the latter part of the list were recalled; this pattern was consistent with an attentional explanation to the extent that attention diminishes towards the latter part of the list. Similarly, Rusted and Eaton-Williams83 found that nicotine-induced accuracy improvements in word recall was related to the length of the word list. That is, a greater improvement was observed after presentation of a 30-item word list, than a 10-item word list. Nicotine delivered by a transdermal patch has also been shown to enhance performance in a Random Letter Generation task (e.g., participants required to name letters of the alphabet in a random order) and a Stroop test (e.g., participants required to read the ink color of color words), presumably by enhancing attentional processes.59
Nonhuman animal studies have also focused on nAChR involvement in attentional processes. The five-choice serial reaction time (5-CSRT) task has been used in rodents to assess the role of various nicotinic agonists and antagonists in attentional processes. Commonly, the apparatus used for this task includes a wall with five distinct holes, each with a light at the rear of the hole. During training, one of the five holes is illuminated for a brief duration. A correct response is registered for nose pokes during the period that the light is illuminated or for a fixed interval after the offset of the light. Daily training sessions usually include about 100 trials (i.e., random light illuminations). Thus, accurate performance in this task involves sustained attention and vigilance throughout the entire session.
Mirza and Stolerman64 found that increasing the time between each light presentation resulted in a performance decrement, likely because prolonged vigilance was necessary to maintain correct responding. Nicotine administration reversed this deficit suggesting that attentional processes were enhanced. Interestingly, shortening the duration of the stimulus illumination (i.e., weakening the signal strength), decreased correct responding, and increased the latency to make a response.11 According to the authors, this data pattern indicates that information processing, not necessarily attentional processing, is impaired. Under these conditions, nicotine administration did not enhance correct responding. Together these results suggest that stimulation of nAChRs by nicotine can enhance attentional processes, but may not necessarily affect informational processing (see ref. 92 for a review of the effects of nicotine in the 5-CSRT task). Further, using the short duration light stimulus, Blondel et al11 replicated the findings of Mirza and Stolerman64 in that nicotine administration did not affect the number of correct responses. However, the authors did find that nicotine decreased the latency to make a correct response and increased anticipatory responses.
To further assess the role of the specific subunits of the nicotinic receptor that may contribute to attentional processes, Grottick and Higgins41 assessed various compounds in rats that had failed to meet criterion during 5-CSRT task training. Presumably, attentional/vigilance processes in these rats were slightly impaired given that they had failed to meet the predetermined criterion. Rats were administered nicotine, AR-R 17779 (an a7* agonist), or SIB 1765F
(an a4p2* agonist). Both nicotine and SIB 1765F improved performance by increasing correct responding and enhancing reaction time. In contrast, AR-R 17779 did not affect correct responding. This data pattern was taken to suggest involvement of the a4p2, but not the a7 subunits, in mediating increased attention/vigilance. Additionally, SIB-1553A, a p4* nAChR agonist, had no effect on correct responding in the 5-CSRT task in aged rats, whereas performance in aged rats was enhanced by nicotine administration.43 Taken together this work suggests that the p4* nAChR is not involved in attentional processes as measured in a 5-CSRT task.
In sum, performance on tasks designed to measure attention processes can be enhanced by stimulation of nicotinic receptors. Specifically, the a4 and P2 subunits appear to contribute to this enhancing effect. Notably, researchers have begun to examine the feasibility of using nAChR compounds as potential therapeutic agents for attention deficit/hyperactivity disorder (ADHD). Nicotine delivered by a transdermal patch to adults with ADHD showed some effect in aiding attentional processes;58 however, further research in this area is required.
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