Chronic nicotine improves cognitive performance in a test of attention but does not attenuate cognitive disruption induced by repeated phencyclidine administration
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Nicotine-induced cognitive enhancement may be a factor maintaining tobacco smoking, particularly in psychiatric populations suffering from cognitive deficits. Schizophrenia patients exhibit higher smoking rates compared with the general population, suggesting that attempts to self-medicate cognitive schizophrenia deficits may underlie these high smoking levels.
The present study explored pro-cognitive effects of nicotine in a model of schizophrenia-like cognitive dysfunction to test this self-medication hypothesis.
Materials and methods
We investigated whether chronic nicotine (3.16 mg/kg/day, base) would attenuate the performance disruption in the five-choice serial reaction time task (5-CSRTT, a task assessing various cognitive modalities, including attention) induced by repeated administration of phencyclidine (PCP), an N-methyl-d-aspartate receptor antagonist that induces cognitive deficits relevant to schizophrenia.
Chronic nicotine administration shortened 5-CSRTT response latencies under baseline conditions. Nicotine-treated rats also made more correct responses and fewer omissions than vehicle-treated rats. Replicating previous studies, repeated PCP administration (2 mg/kg, 30 min before behavioral testing for two consecutive days followed 2 weeks later by five consecutive days of PCP administration) decreased accuracy and increased response latencies, premature responding, and timeout responding. Chronic nicotine did not attenuate these PCP-induced disruptions.
Chronic nicotine had pro-cognitive effects by itself, supporting the hypothesis that cognitive enhancement may contribute to tobacco smoking. At the doses of nicotine and PCP used, however, no support was found for the hypothesis that the beneficial effects of nicotine on cognitive deficits induced by repeated PCP administration, assessed in the 5-CSRTT, are larger than nicotine effects in the absence of PCP.
KeywordsCognition Schizophrenia Nicotine Phencyclidine Attention Processing speed 5-CSRTT Rat
Supported by the National Institute of Mental Health grant MH062527 and Tobacco-Related Disease Research Program (TRDRP) grant 15RT-0022 from the State of California to AM and TRDRP Individual Pre-doctoral Fellowship 15DT-0048 from the State of California to NA. The authors would like to thank Dr. Svetlana Semenova for intellectual input to this work, Mrs. Jessica Benedict and Ms. Chelsea Onifer for technical assistance, Mr. Pete Sharp for excellent assistance with electronics and computer software, and Mr. Mike Arends for outstanding editorial assistance.
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