Chronic nicotine exposure attenuates the effects of Δ9 -tetrahydrocannabinol on anxiety-related behavior and social interaction in adult male and female rats.
Laurie A Manwell, Tanya Miladinovic, Elana Raaphorst, Shadna Rana, Sarah Malecki, Paul E Mallet
Brain and Behavior November 2019 DOI: 10.1002/brb3.1375 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 96 |
| Population | Male and female adult Sprague-Dawley rats |
| Intervention | Nicotine |
| Dose | Nicotine 1 mg/kg, i.p.; THC 0.5, 2.0, or 5.0 mg/kg, i.p. |
| Duration | 14-day nicotine pretreatment, 14-day drug-free period, then acute THC challenge on test day |
| Measures | Emergence (EM) test, elevated plus maze (EPM), social interaction (SI) test |
| Topics | Anxiety Cannabis |
| Keywords | Anxiety-related behavior Cross-sensitization Delta-9-tetrahydrocannabinol Drug abuse Nicotine Social interaction |
| Key findings | THC dose-dependently altered locomotor activity, exploratory behavior, and social interaction, with these effects generally greater in females than males, except for grooming a conspecific. Prior chronic nicotine exposure attenuated some THC effects, specifically locomotor activity in the elevated plus maze and direct but not indirect physical interaction in the social interaction test. The authors suggest this indicates chronic nicotine may induce neuroplastic changes that alter subsequent responses to acute THC. |
Abstract
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. 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. 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. 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.
Comparable studies
Other preclinical and animal studies on cannabis for anxiety, most cited first.