Thesis
Developing A Translationally Relevant Preclinical Model of Cannabis Self-Administration
Washington State University
Master of Science (MS), Washington State University
2018
Handle:
https://hdl.handle.net/2376/101678
Abstract
Increasing use of recreational cannabis (Cannabis sativa) among humans underscores the need for a translationally relevant preclinical model of cannabis self-administration. Researchers studying the effects of cannabis in rodents commonly employ intravenous or intraperitoneal administration routes, which have different pharmacodynamics and pharmacokinetic effects from one another and from vapor administration, the route of choice in humans. Furthermore, researchers frequently study the main psychoactive constituent of cannabis, D9-tetrahydrocannabinol, rather than cannabis itself. Humans typically use dried, whole-plants, and are exposed to over 400 compounds present in cannabis. Therefore, rodent studies using single constituents (e.g., D9-tetrahydrocannabinol or cannabidiol) administered intravenously or intraperitoneally may not adequately predict the consequences of cannabis use in humans. In this thesis, I tested a novel rat model of cannabis-seeking behavior, using response-contingent vapor rewards containing whole-plant extracts. Male Sprague-Dawley rats were trained to self-administer either D9-tetrahydrocannabinol-rich cannabis extract (THCE), or cannabidiol-rich cannabis extract (CBDE), or vehicle (VEH). Rats self-administered their assigned drug for 19 days, and then underwent extinction sessions until drug-seeking was extinguished to a pre-determined criterion. Following extinction, rats underwent subsequent cue-induced reinstatement, where a light cue previously associated with drug delivery was presented at the beginning of the session. During self-administration, THCE and CBDE rats received significantly fewer rewards than VEH rats, but had a higher percentage of active nosepokes. During extinction, responses on active nosepokes decreased across sessions in THCE rats, whereas CBDE rats continued to respond predominately on the active nosepoke. During cue-induced reinstatement, THCE rats responded more on the active nosepoke than VEH rats. Furthermore, self-administration of THCE was dose-dependently attenuated following the administration of the type-1 endogenous cannabinoid (CB1) receptor antagonist AM251. These results indicate that rodents can learn a nosepoke contingency to self-administer whole-plant cannabis extracts, and that this behavior is likely mediated by CB1 receptors. Furthermore, THCE rats change their cannabis-seeking strategy during extinction, while CBDE rats continued to respond on the active nosepoke, perseverating learned behavior. Cannabis-seeking behavior is reinstated in THCE rats following the presentation of a drug-paired cue. Altogether, this paradigm shows enormous promise as a preclinical model of cannabis-seeking.
Metrics
Details
- Title
- Developing A Translationally Relevant Preclinical Model of Cannabis Self-Administration
- Creators
- Lydia Noel Baxter-Potter
- Contributors
- Ryan Joseph McLaughlin (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525101301842
- Language
- English
- Resource Type
- Thesis