Chronic nicotine improves cognitive performance in a test of attention but does not attenuate cognitive disruption induced by repeated phencyclidine administration

Abstract

Rationale: 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.

Objectives: 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.

Results: 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.

Conclusions: 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.

Figure 1

Diagram of experimental design.

Figure 2

Effects of chronic nicotine administration on attentional performance in the 5-CSRTT under baseline conditions and during repeated PCP administration. Accuracy (a), percent correct responses (b), and percent omissions (c) are expressed as mean ± SEM. Bar graphs show binned averages from the 5 baseline days preceding any drug treatment and the 9 days of PCP-free pump treatment (left) and binned averages from the 5 days of saline injection during pump treatment and the 5 days of PCP administration during pump treatment (right). *p < 0.05, statistically significant differences compared with baseline performance. ^††p < 0.01, statistically significant Presence of Pump × Pump Content interaction. ^###p < 0.001, statistically significant difference compared with performance after saline injections. Gray field indicates the period of pump treatment. ↑ indicates a PCP injection.

Figure 3

Effects of chronic nicotine administration on speed of processing in the 5-CSRTT under baseline conditions and during repeated PCP administration. Latencies to correct response are expressed as mean ± SEM. Bar graphs show binned averages from the 5 baseline days preceding any drug treatment and the 9 days of PCP-free pump treatment (left) and binned averages from the 5 days of saline injection during pump treatment and the 5 days of PCP administration during pump treatment (right). ^†p < 0.05, statistically significant Presence of Pump × Pump Content interaction. ^###p < 0.001, statistically significant difference compared with performance after saline injections. Gray field indicates the period of pump treatment. ↑ indicates a PCP injection.

Figure 4

Effects of chronic nicotine administration on inhibition of inappropriate responding in the 5-CSRTT under baseline conditions and during repeated PCP administration. Premature responses are expressed as mean ± SEM. Bar graphs show binned averages from the 5 baseline days preceding any drug treatment and the 9 days of PCP-free pump treatment (left) and binned averages from the 5 days of saline injection during pump treatment and the 5 days of PCP administration during pump treatment (right). *p < 0.05, statistically significant differences compared with baseline performance. ^###p < 0.001, statistically significant difference compared with performance after saline injections. Gray field indicates the period of pump treatment. ↑ indicates a PCP injection.