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Experimenter administered Δ9-THC decreases nicotine self-administration in a rat model.

Antony D Abraham, Jenny L Wiley, Julie A. Marusich

Pharmacology, Biochemistry, and Behavior October 2023 DOI: 10.1016/j.pbb.2023.173632 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Population Adult male and female Sprague-Dawley rats
Interventions Delta-9-tetrahydrocannabinol (THC) Nicotine
Dose 0, 3, 30 mg/kg THC
Duration 14 days of THC treatment prior to and during training, followed by several weeks of self-administration
Topics Cannabis
Keywords Co-abuse Delta-9-tetrahydrocannabinol Nicotine Polysubstance use Self-administration
Key findings Post-session THC decreased nicotine self-administration in male and female rats during acquisition and maintenance, increased the latency to stable nicotine intake, and shifted nicotine dose-effect curves downward, while not affecting sucrose responding. Pre-session THC suppressed responding at higher nicotine doses but also decreased sucrose responding, indicating a nonspecific effect. The authors conclude that THC modulates patterns of nicotine intake in rat models.

Abstract

The co-use of nicotine and cannabis has been steadily rising in the United States. Rodent studies suggest that delta-9-tetrahydrocannabinol (THC) could increase addictive qualities of nicotine, but whether repeated THC exposure alters self-administration of nicotine has not been tested. We hypothesized that THC would increase the reinforcing effects of nicotine and alter nicotine intake. Adult male and female Sprague-Dawley rats were treated with THC (0, 3, 30 mg/kg) daily for 14 days prior to and during training for intravenous self-administration of nicotine. Rats were allowed to self-administer nicotine for several weeks, then tested for sensitivity to nicotine dose through multiple determinations of a nicotine dose-effect curve with or without THC pretreatment. A separate set of rats were trained on fixed ratio responding for sucrose and assessed for THC effects on behavior. Post-session THC decreased nicotine self-administration in male and female rats throughout acquisition and maintenance and increased the latency to stable rates of nicotine intake during acquisition. Post-session THC shifted nicotine dose-effect curves downward, and pre-session THC suppressed responding at higher nicotine doses. Unlike nicotine, responding for sucrose was not affected by post-session THC. Pre-session THC decreased responding for sucrose, particularly for THC-naïve rats. Repeated post-session THC decreased nicotine-taking behaviors but did not alter sucrose responding. Thus, post-session THC may alter sensitivity to nicotine. Pre-session THC treatment decreased lever pressing in both sucrose and nicotine studies, indicating this effect was nonspecific. These studies show that THC modulates patterns of nicotine intake in rat models.

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Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
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Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

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