Chronic nicotine exposure attenuates the effects of Δ(9)‐tetrahydrocannabinol on anxiety‐related behavior and social interaction in adult male and female rats

INTRODUCTION: Anxiogenic and anxiolytic effects of cannabinoids are mediated by different mechanisms, including neural signaling via cannabinoid receptors (CBRs) and nicotinic cholinergic receptors (nAChRs). This study examined the effects of prior nicotine (the psychoactive component in tobacco) exposure on behavioral sensitivity to delta‐9‐tetrahydrocannabinol (THC; the psychoactive component of cannabis) challenge in animals. METHODS: Male and female adult Sprague‐Dawley rats (N = 96) were injected daily with nicotine (1 mg/kg, i.p.) or vehicle for 14 days, followed by a 14‐day drug‐free period. On test day, rats were injected with THC (0.5, 2.0, or 5.0 mg/kg, i.p.) or vehicle and anxiety‐related behavior was assessed in the emergence (EM), elevated plus maze (EPM), and social interaction (SI) tests. RESULTS: Chronic nicotine pretreatment attenuated some of the anxiogenic effects induced by THC challenge which can be summarized as follows: (a) THC dose‐dependently affected locomotor activity, exploratory behavior, and social interaction in the EM, EPM, and SI tests of unconditioned anxiety; (b) these effects of acute THC challenge were greater in females compared with males except for grooming a conspecific; (c) prior nicotine exposure attenuated the effects of acute THC challenge for locomotor activity in the EPM test; and (d) prior nicotine exposure attenuated the effects of THC challenge for direct but not indirect physical interaction in the SI tests. CONCLUSIONS: The ability of nicotine prior exposure to produce long‐lasting changes that alter the effects of acute THC administration suggests that chronic nicotine may induce neuroplastic changes that influence the subsequent response to novel THC exposure.