SEX DIFFERENCES ON THE NICOTINE-INDUCED CONDITIONED PLACE PREFERENCE PARADIGM

Nicotine (NIC) abuse is one of the most prevalent substance use disorders and a reemerging public health issue with the introduction of e-cigarettes and vaping. Smoking prevalence among males is higher than in females, and several sociological reasons are hypothesized to contribute to this phenomenon. Biological differences between sexes in NIC response may contribute, but they are still poorly understood. Moreover, protocols for conditioned place preference (CPP), one of the most common tests to assess NIC-rewarding effects, vary significantly, making data comparison challenging. In this context, our goal is to comparatively assess male and female mice’s responses to NIC using the CPP paradigm. Adult (PND > 70) male and female Swiss mice were subjected to a 9-day unbiased CPP protocol. On day 1, animals underwent a pre-conditioning session to assess basal compartment preference. The conditioning stage occurred on days 2-8, with two daily sessions where mice were either administered NIC (0.05, 0.1, 0.5 mg/kg) or saline paired with one of the compartments. Sessions were conducted so mice were exposed to both NIC and saline daily. The post-conditioning session was held on day 9, where animals moved freely through the apparatus. Place preference was assessed by comparing the time spent in the conditioned compartment between pre- and post-conditioning sessions. NIC induced a bell-shaped dose-effect curve in CPP in both sexes, where the 0,1 mg/kg dose only led to place preference. Interestingly, only female mice exposed to NIC at 0,05 or 0,1 mg/kg displayed hyperlocomotion between test days (pre vs. post), while males exposed to NIC 0,5 mg/kg had fewer total compartment entries in the post-conditioning test. These results hint at a differential nicotine withdrawal effect after a 7-day exposition protocol between sexes. Additional data analyses are being conducted to investigate the locomotor profile during NIC conditioning. Funding: CAPES, CNPq, FAPERJ.