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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Cannabis; Co-abuse; Delta-9-tetrahydrocannabinol; Nicotine; Polysubstance use; Self-administration.

Figure 1.

Acquisition of nicotine self-administration (30 μg/kg/infusion). Mean infusions earned as a function of session and FR value. Data for males are shown in the top panel and data for females are shown in the bottom panel. * indicates significant difference from 0 mg/kg THC group for FR5 (main effect of THC group) (p < 0.05). n=8/group for males and n=7/group for females.

Figure 2.

Infusions earned during nicotine dose-effect curves with no pretreatment (Panels A-B) and 0.3 mg/kg THC pretreatment (Panels C-D). Data from males are shown in left panels and data from females are shown in right panels. S = saline, TV = self-administration of 30 μg/kg/infusion nicotine + THC vehicle pretreat. * = significant difference from 0 mg/kg THC group (main effect of THC group); # = significant difference from saline (main effect of nicotine dose) (p < 0.05). n=7/sex/group except that n=8/group for 3 and 30 THC males.

Figure 3.

Infusions earned during nicotine dose-effect curves with 3 mg/kg THC pretreatment (Panels A-B) and 30 mg/kg THC pretreatment (Panels C-D). Data from males are shown in left panels and data from females are shown in right panels. S = saline, TV = self-administration of 30 μg/kg/infusion nicotine + THC vehicle pretreat. For no pretreatment and 0.3 THC pretreatment, n=8 in Panels C and E, and n=7 in Panels A, B, D, and F; for 3 and 30 mg/kg THC pretreatment, n=6 in Panels A, B, and D, n=4 in Panel F; n=8 for 3 THC pretreatment in Panels C and E, and n=7 for 30 THC pretreatment in Panels C and E.

Figure 4.

Acquisition of sucrose self-administration. Mean pellets earned as a function of session and FR value. Data for males are shown in the top panel and data for females are shown in the bottom panel. n=8/sex/group.

Figure 5.

Pellets earned during sucrose self-administration sessions with no pretreatment (Panels A-B) and 0.3 mg/kg THC pretreatment (Panels C-D). Data from males are shown in left panels and data from females are shown in right panels. TV = sucrose self-administration + THC vehicle pretreat. * = significant difference from 0 mg/kg THC group (main effect of THC group); @ = significant difference from male (main effect of sex); % = significant difference from THC vehicle (sex x pretreat interaction) (p < 0.05). n=8/sex/group, except that n=7 for 3 THC males and n=6 for 30 THC males.

Figure 6.

Pellets earned during sucrose self-administration sessions with 3 mg/kg THC (Panels A-B) and 30 mg/kg THC pretreatment (Panels C-D). Data from males are shown in left panels and data from females are shown in right panels. TV = sucrose self-administration + THC vehicle pretreat. * = significant difference from 0 mg/kg THC group (main effect of THC group); % = significant difference from THC vehicle (sex x pretreat interaction) (p < 0.05). n=8 in Panels A, B, D; n=7 in Panel C; n=6 in Panel E except for 30 THC pretreatment, which was n=5; n=8 in Panel F except for 30 THC pretreatment, which was n=7.