Afferent-specific AMPA receptor subunit composition and regulation of synaptic plasticity in midbrain dopamine neurons by abused drugs.
Cameron H Good, Carl R. Lupica
Journal of Neuroscience June 9, 2010 DOI: 10.1523/jneurosci.1507-10.2010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Ex vivo electrophysiology study in rat brain slices Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Cocaine Delta(9)-tetrahydrocannabinol (Delta(9)-THC) AM251 |
| Duration | 24 hours after single injections |
| Measures | EPSCs, long-term depression (LTD) |
| Topics | Neuroplasticity |
| Key points | A single cocaine injection increased GluR2-lacking AMPA receptors at both PPN and local VTA glutamate synapses onto VTA dopamine neurons, permitting LTD at both, whereas a single Delta(9)-THC injection increased these receptors and permitted LTD only at the PPN pathway. The authors argue that different abused drugs may influence distinct glutamatergic afferents to VTA dopamine neurons, possibly relating to different reinforcing or addictive properties. |
Abstract
Ventral tegmental area (VTA) dopamine (DA) neurons play a pivotal role in processing reward-related information and are involved in drug addiction and mental illness in humans. Information is conveyed to the VTA in large part by glutamatergic afferents that arise in various brain nuclei, including the pedunculopontine nucleus (PPN). Using a unique rat brain slice preparation, we found that PPN stimulation activates afferents targeting GluR2-containing AMPA receptors (AMPAR) on VTA DA neurons, and these afferents did not exhibit long-term depression (LTD). In contrast, activation of glutamate afferents onto the same DA neurons via stimulation within the VTA evoked EPSCs mediated by GluR2-lacking AMPARs that demonstrated LTD or EPSCs mediated by GluR2-containing AMPA receptors that did not express LTD. Twenty-four hours after single cocaine injections to rats, GluR2-lacking AMPARs were increased at both PPN and local VTA projections, and this permitted LTD expression in both pathways. Single injections with the main psychoactive ingredient of marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), increased GluR2-lacking AMPA receptors and permitted LTD in only the PPN pathway, and these effects were prevented by in vivo pretreatment with the cannabinoid CB1 receptor antagonist AM251. These results demonstrate that cocaine more globally increases GluR2-lacking AMPA receptors at all glutamate synapses on VTA dopamine neurons, whereas Delta(9)-THC selectively increased GluR2-lacking AMPA receptors at subcortical PPN synapses. This suggests that different abused drugs may exert influence over distinct sets of glutamatergic afferents to VTA DA neurons which may be associated with different reinforcing or addictive properties of these drugs.
Comparable studies
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| N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice | 2020 | In vitro and in vivo experimental study |
Citations in the library
Cited by 3
- Three-day delta-9-tetrahydrocannabinol (THC) exposure eliminates long-term depression in ventral tegmental area of young, but not adult mice. Journal of Cannabis Research May 31, 2025
- Impairment of Synaptic Plasticity by Cannabis, Δ9-THC, and Synthetic Cannabinoids. Cold Spring Harbor perspectives in medicine May 3, 2021
- Cannabinoid modulation of drug reward and the implications of marijuana legalization. Brain Research December 2, 2015