Changes in striatal dopamine release, sleep, and behavior during spontaneous Δ-9-tetrahydrocannabinol abstinence in male and female mice.
Andrew J Kesner, Yolanda Mateo, Karina P Abrahao, Stephanie Ramos-Maciel, Matthew J Pava, Alexa L Gracias, Riley T Paulsen, Hartley B Carlson, David M Lovinger
Neuropsychopharmacology July 2022 DOI: 10.1038/s41386-022-01326-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice chronically treated with THC |
| Intervention | delta-9-tetrahydrocannabinol (THC) |
| Topics | Cannabis |
| Key points | Chronic THC treatment followed by abstinence altered electrically elicited striatal dopamine release, produced sleep disturbances resembling clinical observations, and caused affect-related behavioral changes in mice. These withdrawal-associated changes were more consistently observed in male mice, according to the authors. |
Abstract
Withdrawal symptoms are observed upon cessation of cannabis use in humans. Although animal studies have examined withdrawal symptoms following exposure to delta-9-tetrahydrocannabinol (THC), difficulties in obtaining objective measures of spontaneous withdrawal using paradigms that mimic cessation of use in humans have slowed research. The neuromodulator dopamine (DA) is affected by chronic THC treatment and plays a role in many behaviors related to human THC withdrawal symptoms. These symptoms include sleep disturbances that often drive relapse, and emotional behaviors like irritability and anhedonia. We examined THC withdrawal-induced changes in striatal DA release and the extent to which sleep disruption and behavioral maladaptation manifest during abstinence in a mouse model of chronic THC exposure. Using a THC treatment regimen known to produce tolerance, we measured electrically elicited DA release in acute brain slices from different striatal subregions during early and late THC abstinence. Long-term polysomnographic recordings from mice were used to assess vigilance state and sleep architecture before, during, and after THC treatment. We additionally assessed how behaviors that model human withdrawal symptoms are altered by chronic THC treatment in early and late abstinence. We detected altered striatal DA release, sleep disturbances that mimic clinical observations, and behavioral maladaptation in mice following tolerance to THC. Altered striatal DA release, sleep, and affect-related behaviors associated with spontaneous THC abstinence were more consistently observed in male mice. These findings provide a foundation for preclinical study of directly translatable non-precipitated THC withdrawal symptoms and the neural mechanisms that affect them.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 6
- Tolerance, physical dependence, and Δ9-THC-like interoceptive effects of cannabinol in mice. Drug and Alcohol Dependence September 1, 2026
- Prior cannabis vapor exposure impairs pattern separation in rodents of multiple ages but is rescued by citicoline administration. Neuroscience May 25, 2026
- Repeated Tetrahydrocannabinol Injections Induce Tolerance but Do Not Disrupt Ongoing Behaviour Upon Withdrawal in Male and Female Rats With Inflammatory Pain. European Journal of Pain May 1, 2026
- Tolerance but No Spontaneous Withdrawal Following Repeated THC Injections in Male and Female Rats Cannabis and Cannabinoid Research December 1, 2025
- Psychosis associated with cannabis withdrawal: systematic review and case series The British Journal of Psychiatry December 3, 2024
and 1 more in the library
Cites 7
- Subcortical Local Functional Hyperconnectivity in Cannabis Dependence Biological Psychiatry: Cognitive Neuroscience and Neuroimaging November 23, 2017
- Novel behavioral assays of spontaneous and precipitated THC withdrawal in mice. Drug and Alcohol Dependence October 1, 2018
- EEG of chronic marijuana users during abstinence: relationship to years of marijuana use, cerebral blood flow and thyroid function. Clinical Neurophysiology February 2008
- Marijuana abstinence effects in marijuana smokers maintained in their home environment. Archives of General Psychiatry October 2001
- Abstinence symptoms following oral THC administration to humans. Psychopharmacology February 1, 1999
and 2 more in the library