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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:asrf-2163 |
| Date | 25 April 2023 |
| Creators | Ahmed, Cristal, Walston, Kynah B, Jackson, Alex B, Palmatier, Matthew I. |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | Appalachian Student Research Forum |
Page generated in 0.0017 seconds