Delta9-tetrahydrocannabinol is a full agonist at CB1 receptors on GABA neuron axon terminals in the hippocampus.
Nora Laaris, Cameron H Good, Carl R. Lupica
Neuropharmacology 2010 DOI: 10.1016/j.neuropharm.2010.04.013 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Whole-cell electrophysiology in brain slices from C57BL6/J mice Peer reviewed |
|---|---|
| Population | C57BL6/J mice, including wildtype and CB1 receptor knockout mice |
| Interventions | WIN55 212-2 |
| Topics | Cannabis |
| Key points | THC inhibited synaptic GABA IPSCs in mouse hippocampal neurons in a CB1 receptor-dependent manner, with effects dependent on the vehicle used. THC did not alter photolysis-evoked GABA currents, and its maximal effect was similar to the full agonist WIN55,212-2, indicating THC acts as a full agonist at CB1 receptors on GABA axon terminals. |
Abstract
Marijuana impairs learning and memory through actions of its psychoactive constituent, delta-9-tetrahydrocannabinol (Delta(9)-THC), in the hippocampus, through activation of cannabinoid CB1 receptors (CB1R). CB1Rs are found on glutamate and GABA neuron axon terminals in the hippocampus where they control neurotransmitter release. Previous studies suggest that Delta(9)-THC is a partial agonist of CB1Rs on glutamate axon terminals in the hippocampus, whereas its effects on GABA terminals have not been described. Using whole-cell electrophysiology in brain slices from C57BL6/J mice, we examined Delta(9)-THC effects on synaptic GABA IPSCs and postsynaptic GABA currents elicited by laser-induced photo-uncaging (photolysis) of alpha-carboxy-2-nitrobenzyl (CNB) caged GABA. Despite robust inhibition of synaptic IPSCs in wildtype mice by the full synthetic agonist WIN55,212-2, using a Tween-80 and DMSO vehicle, Delta(9)-THC had no effects on IPSCs in this, or in a low concentration of another vehicle, randomly-methylated beta-cyclodextrin (RAMEB, 0.023%). However, IPSCs were inhibited by Delta(9)-THC in 0.1% RAMEB, but not in neurons from CB1R knockout mice. Whereas Delta(9)-THC did not affect photolysis-evoked GABA currents, these responses were prolonged by a GABA uptake inhibitor. Concentration-response curves revealed that the maximal effects of Delta(9)-THC and WIN55,212-2 were similar, indicating that Delta(9)-THC is a full agonist at CB1Rs on GABA axon terminals. These results suggest that Delta(9)-THC inhibits GABA release, but does not directly alter GABA(A) receptors or GABA uptake in the hippocampus. Furthermore, full agonist effects of Delta(9)-THC on IPSCs likely result from a much higher expression of CB1Rs on GABA versus glutamate axon terminals in the hippocampus.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Disruption of hippocampal synaptic transmission and long‐term potentiation by psychoactive synthetic cannabinoid ‘Spice’ compounds: comparison with Δ9‐tetrahydrocannabinol Addiction Biology January 5, 2016
- Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis Psychopharmacology October 13, 2022
- Impaired mnemonic pattern separation associated with PTSD symptoms paradoxically improves with regular cannabis use npj Mental Health Research April 24, 2025
- Adolescent Δ-9-tetrahydrocannabinol exposure induces differential acute and long-term neuronal and molecular disturbances in dorsal vs. ventral hippocampal subregions. Neuropsychopharmacology February 2023
- Vaporized Delta-9-tetrahydrocannabinol Inhalation in Female Sprague Dawley Rats: A Pharmacokinetic and Behavioral Assessment. Current Pharmaceutical Design 2023
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Cites 7
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and 2 more in the library