ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Neurosteroid Agonist at GABAA receptor induces persistent neuroplasticity in VTA dopamine neurons.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone.Biology of sex differences · 2022Trial
- Neurosteroid Modulation of Synaptic and Extrasynaptic GABABiomolecules · 2024Article
- Alprazolam exposure during adolescence induces long-lasting dysregulation in reward sensitivity to morphine and second messenger signaling in the VTA-NAc pathway.Scientific reports · 2023Article
- Article
- Rapid onset brain plasticity at novel pharmacologic targets hypothetically drives innovations for rapid onset antidepressant actions.Journal of psychopharmacology (Oxford, England) · 2023Article
- Estrous Cycle Mediates Midbrain Neuron Excitability Altering Social Behavior upon Stress.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Discontinuation of hormonal contraception due to changes in mood and decreases in sexual desire: the role of adverse childhood experiences.The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception · 2022Article
- Muscimol Directly Activates the TREK-2 Channel Expressed in GABAergic Neurons through Its N-Terminus.International journal of molecular sciences · 2021Article
- Tonic GABAergic inhibition, via GABAThe European journal of neuroscience · 2021Article
- Heterogeneous somatostatin-expressing neuron population in mouse ventral tegmental area.eLife · 2020Article
- Allopregnanolone Decreases Evoked Dopamine Release Differently in Rats by Sex and Estrous Stage.Frontiers in pharmacology · 2020Article
- Conditioned Aversion and Neuroplasticity Induced by a Superagonist of Extrasynaptic GABAFrontiers in molecular neuroscience · 2019Article
- Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders.Frontiers in endocrinology · 2019Review
- Examining the effects of alcohol on GABAAlcohol (Fayetteville, N.Y.) · 2018Article
- Ventral Tegmental Area GABA Neurons Are Resistant to GABA(A) Receptor-Mediated Inhibition During Ethanol Withdrawal.Frontiers in neuroscience · 2018Article
- Activation of extrasynaptic δ-GABAHormones and behavior · 2017Article
- Comparing the discriminative stimulus effects of modulators of GABAA receptors containing α4-δ subunits with those of gaboxadol in rats.Psychopharmacology · 2016Article
- Effects of the neuroactive steroid allopregnanolone on intracranial self-stimulation in C57BL/6J mice.Psychopharmacology · 2014Article
- GABAA receptor drugs and neuronal plasticity in reward and aversion: focus on the ventral tegmental area.Frontiers in pharmacology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The main fast-acting inhibitory receptors in the mammalian brain are γ-aminobutyric acid type-A (GABAA) receptors for which neurosteroids, a subclass of steroids synthesized de novo in the brain, constitute a group of endogenous ligands with the most potent positive modulatory actions known. Neurosteroids can act on all subtypes of GABAA receptors, with a preference for δ-subunit-containing receptors that mediate extrasynaptic tonic inhibition. Pathological conditions characterized by emotional and motivational disturbances are often associated with perturbation in the levels of endogenous neurosteroids. We studied the effects of ganaxolone (GAN)-a synthetic analog of endogenous allopregnanolone that lacks activity on nuclear steroid receptors-on the mesolimbic dopamine (DA) system involved in emotions and motivation. A single dose of GAN in young mice induced a dose-dependent, long-lasting neuroplasticity of glutamate synapses of DA neurons ex vivo in the ventral tegmental area (VTA). Increased α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N-methyl-D-aspartate ratio and rectification of AMPA receptor responses even at 6 days after GAN administration suggested persistent synaptic targeting of GluA2-lacking AMPA receptors. This glutamate neuroplasticity was not observed in GABAA receptor δ-subunit-knockout (δ-KO) mice. GAN (500 nM) applied locally to VTA selectively increased tonic inhibition of GABA interneurons and triggered potentiation of DA neurons within 4 h in vitro. Place-conditioning experiments in adult wild-type C57BL/6J and δ-KO mice revealed aversive properties of repeated GAN administration that were dependent on the δ-subunits. Prolonged neuroadaptation to neurosteroids in the VTA might contribute to both the physiology and pathophysiology underlying processes and changes in motivation, mood, cognition, and drug addiction.
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