0027 Ravaged Rat Rhythms: Circadian Rhythm Influence on Mecamylamine-Induced Nicotine Withdrawal

Abstract

Abstract Introduction Mecamylamine (Mec) is a nicotinic acetylcholine receptor (nAChR) antagonist, serving as an important piece of nicotine addiction cessation therapies. When co-administered with nicotine, Mec blocks the positive reinforcing effects of the substance of abuse and may promote a lessened desire to perpetuate an addictive cycle. On the other hand, the magnitude of the withdrawal symptoms caused by this co-administration may reinforce addiction as users can choose to terminate the process of quitting. Methods The present study uses Sprague-Dawley rats to examine if the time of withdrawal onset in relation to circadian rhythms impacts the magnitude of the relevant aversive symptoms. We hypothesized that Mec injected during the rat’s dark period show significantly less aversive symptoms when compared to when it’s done during their light period. For this, we injected rats (n=3 per group) twice a day for thirteen days subcutaneously, with either saline or nicotine, a validated protocol to induce addiction. To measure aversive symptoms of nicotine precipitated withdrawal in light vs dark periods, we used a conditioned place aversion (CPA) behavioral assay in which the rats were either tested mid-light or mid-dark periods. In CPA, the rats were first introduced to the two distinct chambers and allowed to freely move in between them (day 10, for 15 minutes), while time spent in each one was analyzed. Then, they were conditioned to associate one chamber with saline and the other with Mec (days 11-12, for 30 minutes each). Finally, they were placed again in freedom, and the time spent in the mecamylamine-paired chamber was detracted from pre-conditioning to give us the results of aversion (day 13, for 15 minutes). Results We predicted that in the aftermath, the light-period rats on nicotine addiction schedule would show the shortest change in time in Mec-paired chamber, while saline-scheduled rats across both periods would show a change of zero—or no impact of Mec. Results indicated no significant differences between group averages for time spent in the Mec-paired chamber, but they showed saline-scheduled rats to be similarly aversive to it. Conclusion This result indicates the potential need for a study with a more selective nicotine blocker. Support (if any)