Nicotine-induced Attentional Enhancement in Rats Effects of Chronic Exposure to Nicotine

Abstract

Consistent with human literature, previous studies identified attention-enhancing effects of nicotine in rats, using a 5-choice task. The present study addressed the influence of repeated exposure to nicotine on these effects. Over six weeks, the effects of nicotine (0.0, 0.05 and 0.2 mg/kg) given ten min before sessions were tested each week. In addition, rats were injected daily two hours after sessions. In the first week, when these post-session injections were of saline for all rats, presession nicotine had profound rate-disruptive effects at the larger dose. In weeks 2-6, when half the rats received postsession injections of saline and the other half of nicotine (0.4 mg/kg) Among the beneficial effects of nicotine on human cognitive performance, the most consistent findings have been on attention (Stolerman et al. 1995). Such effects have been reported in non-deprived smokers and non-smokers, suggesting that they were not just due to a mere alleviation of withdrawal-induced deficits (Wesnes and Warburton 1984;Foulds et al. 1996;. A range of therapeutic applications of nicotine may develop from this ability to improve attentional functions. Acutely administered nicotine has been shown to reduce performance deficits of patients with Alzheimer's disease in a task of sustained attention (Sahakian et al. 1989;Jones et al. 1992). There is also some indication that nicotine may be beneficial in attention-deficit/hyperactivity disorder and schizophrenia (Levin et al. 1996a, b).A prerequisite for a chronic therapeutic use of nicotinic compounds as cognitive enhancers is that tolerance does not develop to the effects with repeated administration. When administered to Alzheimer's disease patients over four weeks via transdermal patches, nicotine reduced omission errors in the continuous performance task of attention over the entire course of the treatment (White and Levin 1999). These results are encouraging, but further systematic studies of how nicotine-induced attentional improvements develop with chronic administration are lacking. This may be due to ethical constraints in chronically exposing non-smokers to nicotine The effects of nicotine have been examined in several paradigms for assessing attention in rodents. The 5-choice serial reaction time task (5-CSRTT) requires rats to continuously monitor an array of five holes for the occurrence of brief flashes of light presented randomly in one of the locations. In this paradigm, consistent attentional improvements with systemic nicotine have been reported in unlesioned rats (Mirza and Stolerman 1998;Hahn et al. 2002). These improvements were obtained repeatedly in the same subjects, in contrast to earlier findings by Blondel et al. (1999) where increases in response accuracy disappeared after the first administration of nicotine. Results from another study (Grottick and Higgins 2000) using the 5-CSRTT indicated that the effect was even greater after nicotine pre-exposure (daily injections of 0.2 mg/kg for 20 days or longer).In a different attention task, requirin...

Chronic nicotine administration improves attention while nicotine withdrawal induces performance deficits in the 5-choice serial reaction time task in rats

“…Finally, in the modified 5-CSRTT, initial doses of nicotine disrupted performance (i.e., increased omission errors and decreased premature responses) in Lister Hooded rats tested under conditions that increased attentional demands (i.e., increased ITI and reduced stimulus duration compared to baseline conditions (Hahn and Stolerman, 2002). However, when tolerance developed to these disruptive effects of nicotine, further administration of the drug revealed attentional improvements reflected in increased accuracy, decreased omissions and increased speed of responding (Hahn and Stolerman, 2002).…”

Hypocretin and Nicotine Excite the Same Thalamocortical Synapses in Prefrontal Cortex: Correlation with Improved Attention in Rat

“…The effect of nicotine on divided attention is unusual in that it occurs with both acute and chronic exposure to nicotine (Hahn and Stolerman, 2002) and appears to be mediated by high-affinity ␣4␤2 nicotinic receptors (Blondel et al, 2000;Grottick and Higgins, 2000). In some studies, ␣4␤2 nicotinic receptors on interneurons have been shown to be almost completely desensitized by low levels of nicotine (Wooltorton et al, 2003) [but see Alkondon et al (2000) and Mansvelder et al (2002), which required higher concentrations of nicotine to achieve a similar desensitization].…”

“…Direct infusion of nicotine into the prefrontal cortex in the rat can enhance divided attention to a degree similar to that of systemic nicotine (Hahn et al, 2003). The improvement of attention with nicotine is unusual in that it persists despite chronic use (Hahn and Stolerman, 2002) and may be underappreciated as a reason that people, particularly those who have attentional problems attributable to an underlying psychiatric illness such as schizophrenia, are much more likely to smoke.…”

Neuroplasticity in Cigarette Smokers Is Altered under Withdrawal and Partially Restituted by Nicotine Exposition

“…Beyond the addictive component, nicotine has prominent effects on cognition. Studies in animals and nonsmoking humans have shown improvements in attention, working, and episodic memories (Hahn and Stolerman, 2002;Jubelt et al, 2008;Heishman et al, 2010). In smokers, nicotine withdrawal leads to reduced verbal and working memory capacity, which could be partially replaced by nicotine replacement therapy (Jacobsen et al, 2005;Cole et al, 2010).…”