Three-day delta-9-tetrahydrocannabinol (THC) exposure eliminates long-term depression in ventral tegmental area of young, but not adult mice.
Michael Von Gunten, Seth Hoffman, Addison Smartt, Jeffrey G Edwards
Journal of Cannabis Research May 31, 2025 DOI: 10.1186/s42238-025-00287-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Young (P14-P54) and adult (P66-P240) mice |
| Intervention | delta-9-tetrahydrocannabinol (THC) |
| Duration | 3-day treatment |
| Topics | Cannabis Depression |
| Keywords | Adolescent Faah Gaba Hdac3 Ltd Plasticity Qpcr Real-time quantitative pcr Vta |
| Key findings | Three days of THC treatment eliminated CB1-dependent LTD in VTA GABA cells of young mice but not adult mice. |
Abstract
Ventral tegmental area (VTA) dopamine signaling plays a key role in reward learning and drug dependence. VTA dopamine cell activity is regulated in part by local GABA interneurons, which participate in regulating reward prediction. Previously, our lab identified a cannabinoid type 1 receptor (CB1)-dependent form of excitatory long-term depression (LTD) in VTA GABA cells. LTD was eliminated in both young and adult mice after 7-10-day delta-9-tetrahydrocannabinol (THC) exposure. To build off these previous findings, we used mouse ex vivo brain slices to examine whether young mice undergo THC-induced alterations to VTA GABA cell plasticity after fewer exposures than their adult counterparts, as human adolescents have increased sensitivity to THC. Whole-cell electrophysiological recordings were performed on young (P14-P54) and adult (P66-P240) mice treated with THC or vehicle control for 3 days, after which we attempted to induce CB1-dependent LTD ex vivo. Plasticity was eliminated in young but not adult mice after 3 days of THC treatment. Because our previous work illustrated age-dependent alterations to mRNA transcripts after chronic THC-treatment, we also performed quantitative real-time PCR to assess any age dependent differences of 3-day THC exposure on mRNA levels in the VTA. Quantitative PCR revealed no THC-induced changes for young or adult mice but did show several differences between young and adult control mice. This age-dependent impact of THC on synaptic activity could reveal a physiological mechanism underlying increased sensitivity of adolescents to THC-induced alterations to plasticity.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 10
- Chronic Δ9-tetrahydrocannabinol impact on plasticity, and differential activation requirement for CB1-dependent long-term depression in ventral tegmental area GABA neurons in adult versus young mice. Frontiers in Neuroscience 2022
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- CB1-Dependent Long-Term Depression in Ventral Tegmental Area GABA Neurons: A Novel Target for Marijuana. Journal of Neuroscience November 8, 2017
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