Revisiting the effect of nicotine on interval timing

This paper reviews the evidence for nicotine-induced acceleration of the internal clock when timing in the seconds-to-minutes timescale, and proposes an alternative explanation to this evidence: that nicotine reduces the threshold for responses that result in more reinforcement. These two hypotheses were tested in male Wistar rats using a novel timing task. In this task, rats were trained to seek food at one location after 8s since trial onset and at a different location after 16s. Some rats received the same reward at both times (group SAME); some received a larger reward at 16s (group DIFF). Steady baseline performance was followed by 3 days of subcutaneous nicotine administration (0.3mg/kg), baseline recovery, and an antagonist challenge (mecamylamine, 1.0mg/kg). Nicotine induced a larger, immediate reduction in latencies to switch (LTS) in group DIFF than in group SAME. This effect was sustained throughout nicotine administration. Mecamylamine pretreatment and nicotine discontinuation rapidly recovered baseline performance. These results support a response-threshold account of nicotinic disruption of timing performance, possibly mediated by nicotinic acetylcholine receptors. A detailed analysis of the distribution of LTSs suggests that anomalous effects of nicotine on LTS dispersion may be due to loss of temporal control of behavior.