Pre- and post-nicotine circadian activity rhythms can be differentiated by a paired environmental cue.

Previous studies have shown that addictive drugs presented daily at fixed times produce circadian (oscillator-driven) anticipatory and evoked activity rhythms in rats. Other studies have shown that environmental cues paired with addictive drugs produce tolerance to drug effects and elicit craving behavior when presented without the drug. The present study tested these circadian entrainment and paired-cue conditioning effects together. This study compared the ability of daily nicotine and saline injections at different fixed times to entrain pre-injection (anticipatory) and post-injection (evoked) circadian activity rhythms in two groups of female Sprague-Dawley rats. One group (Paired) had an environmental cue (a tone) paired with the effects of the nicotine injection, and the second group (Unpaired) had the tone paired with the effects of the saline injection. The rats were housed singly for 56 days in chambers with attached wheels under constant dim light and rate-limited food access. During three separate injection phases, nicotine and saline were administered daily at different fixed times, and the tone was presented at the second injection time. Three multi-day test phases examined circadian activity (a) without injections or tone, (b) with the tone alone at normal and novel times, and (c) with the tone absent and with injections occurring at normal and at novel times. The results showed that nicotine entrained both pre- and post-injection circadian oscillators, and the nicotine-paired tone interfered with pre-injection anticipatory activity.