Pharmacological Characterization of the Reinforcement-Related Effects of THC in Male and Female Rats.
Location
Culp Center Ballroom
Start Date
4-25-2023 9:00 AM
End Date
4-25-2023 11:00 AM
Poster Number
153
Faculty Sponsor’s Department
Psychology
Name of Project's Faculty Sponsor
Matthew Palmatier
Additional Sponsors
na
Competition Type
Competitive
Type
Poster Presentation
Project's Category
Psychology
Abstract or Artist's Statement
The popularity of cannabis and reduction of cannabis prohibition in the United States has led to increased consumption in human users. However, relatively little is understood about the abuse potential of cannabis and its main psychoactive ingredient, THC. One reason for the lack of insight into the addictive effects of THC is that the animal models investigating voluntary intake of THC have been hampered by low rates of behavior and THC intake often does not surpass intake of vehicle. We hypothesized that, in addition to supporting operant behavior (smoking, vaping, or consuming edibles) THC might increase the reinforcing effects of non-drug rewards (e.g., playing video games, listening to music, eating snacks). To investigate this hypothesis, we evaluated whether THC injections could increase responding for saccharin (0.2% w/v, SACC) in male and female rats. During our investigation we noted that the pharmacology of THC was complex, with potent motor suppressant effects, and that changes in behavior depended on the pharmacokinetics of THC administration. To further explore the pharmacokinetics, we conducted 3 experiments that manipulated THC dose (Experiment 1), Injection-Test interval (Experiment 2) and Injection-Injection interval (washout duration, Experiment 3). We hypothesized that THC would increase responding for SACC, but that this effect would depend on having a longer time between sessions to reduce motor-suppressing effects of THC accumulation. Male and female rats were shaped to respond for SACC under a progressive ratio (PR) schedule of reinforcement. The PR schedule measures motivation by increasing the response requirement after each reinforcer is earned. In Experiment 1 there was a significant effect of THC dose, with moderate doses (0.3-0.75 mg/kg) increasing motivation for SACC and high doses (3 mg/kg) causing significant motor suppression. In Experiment 2 (Injection-Test interval) we found that the timing of THC injections was critical – enhancing effects were observed soon after THC injections were administered (30-60 min) but after 120 min THC no longer increased motivation for SACC. Finally, in Experiment 3 (Injection-Injection interval) we found that daily injections of THC (24 h washout) resulted in significant decreases in motivation from Session 1 to session 8. In contrast, 72 h washout intervals resulted in stable enhancement of motivation for SACC by THC. These studies indicate that the reinforcement enhancing effects of THC are robust but depend critically on the pharmacokinetics and bioavailability of THC.
Pharmacological Characterization of the Reinforcement-Related Effects of THC in Male and Female Rats.
Culp Center Ballroom
The popularity of cannabis and reduction of cannabis prohibition in the United States has led to increased consumption in human users. However, relatively little is understood about the abuse potential of cannabis and its main psychoactive ingredient, THC. One reason for the lack of insight into the addictive effects of THC is that the animal models investigating voluntary intake of THC have been hampered by low rates of behavior and THC intake often does not surpass intake of vehicle. We hypothesized that, in addition to supporting operant behavior (smoking, vaping, or consuming edibles) THC might increase the reinforcing effects of non-drug rewards (e.g., playing video games, listening to music, eating snacks). To investigate this hypothesis, we evaluated whether THC injections could increase responding for saccharin (0.2% w/v, SACC) in male and female rats. During our investigation we noted that the pharmacology of THC was complex, with potent motor suppressant effects, and that changes in behavior depended on the pharmacokinetics of THC administration. To further explore the pharmacokinetics, we conducted 3 experiments that manipulated THC dose (Experiment 1), Injection-Test interval (Experiment 2) and Injection-Injection interval (washout duration, Experiment 3). We hypothesized that THC would increase responding for SACC, but that this effect would depend on having a longer time between sessions to reduce motor-suppressing effects of THC accumulation. Male and female rats were shaped to respond for SACC under a progressive ratio (PR) schedule of reinforcement. The PR schedule measures motivation by increasing the response requirement after each reinforcer is earned. In Experiment 1 there was a significant effect of THC dose, with moderate doses (0.3-0.75 mg/kg) increasing motivation for SACC and high doses (3 mg/kg) causing significant motor suppression. In Experiment 2 (Injection-Test interval) we found that the timing of THC injections was critical – enhancing effects were observed soon after THC injections were administered (30-60 min) but after 120 min THC no longer increased motivation for SACC. Finally, in Experiment 3 (Injection-Injection interval) we found that daily injections of THC (24 h washout) resulted in significant decreases in motivation from Session 1 to session 8. In contrast, 72 h washout intervals resulted in stable enhancement of motivation for SACC by THC. These studies indicate that the reinforcement enhancing effects of THC are robust but depend critically on the pharmacokinetics and bioavailability of THC.