ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Tonic inhibition of accumbal spiny neurons by extrasynaptic α4βδ GABAA receptors modulates the actions of psychostimulants.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 66 citations in OpenAlex.
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- Plasticity of ventral tegmental area disturbance during abstinence after repeated amphetamine exposure: restoration by selective activation of group II metabotropic glutamate receptors.Frontiers in pharmacology · 2025Article
- Loss of glycine receptors in the nucleus accumbens and ethanol reward in an Alzheimer´s Disease mouse model.Progress in neurobiology · 2024Article
- Neurosteroid Modulation of Synaptic and Extrasynaptic GABABiomolecules · 2024Article
- Mutation of novel ethanol-responsive lncRNA Gm41261 impacts ethanol-related behavioral responses in mice.Genes, brain, and behavior · 2024Article
- Early developmental changes in GABAA receptor expression in nucleus accumbens medium spiny neurons.Frontiers in neuroscience · 2024Article
- Subunit-specific expression and function of AMPA receptors in the mouse locus coeruleus.Journal of anatomy · 2023Article
- GABA tone regulation and its cognitive functions in the brain.Nature reviews. Neuroscience · 2023Review
- α4-Containing GABAeNeuro · 2023Article
- Interaction between maternal immune activation and peripubertal stress in rats: impact on cocaine addiction-like behaviour, morphofunctional brain parameters and striatal transcriptome.Translational psychiatry · 2023Article
- Gamma-aminobutyric acid type A receptor alpha 4 coordinates autophagy, inflammation, and immunometabolism to promote innate immune activation.Autophagy reports · 2023Article
- Navigating the complex landscape of benzodiazepine- and Z-drug diversity: insights from comprehensive FDA adverse event reporting system analysis and beyond.Frontiers in psychiatry · 2023Article
- Generation of Astrocyte-Specific MAOB Conditional Knockout Mouse with Minimal Tonic GABA Inhibition.Experimental neurobiology · 2022Article
- Modulation of dopamine release by ethanol is mediated by atypical GABAAddiction biology · 2022Article
- Allopregnanolone Decreases Evoked Dopamine Release Differently in Rats by Sex and Estrous Stage.Frontiers in pharmacology · 2020Article
- High ethanol sensitive glycine receptors regulate firing in D1 medium spiny neurons in the nucleus accumbens.Neuropharmacology · 2019Article
- Conditioned Aversion and Neuroplasticity Induced by a Superagonist of Extrasynaptic GABAFrontiers in molecular neuroscience · 2019Article
- Early-life adversity selectively impairs α2-GABANeuropharmacology · 2018Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ(-/-) or α4(-/-) mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4(-/-) mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4(D1-/-)) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4(-/-) or α4(D1-/-) mice, blocked cocaine enhancement of CPP. In comparison, α4(D2-/-) mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.