GABAB Receptor Functions in the Mesolimbic Dopamine System

Lalive, Arnaud L.; Lüscher, Christian

doi:10.1007/978-3-319-46044-4_8

Cited by 8 publications

(3 citation statements)

References 117 publications

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“…GABA manipulations in experimental animals have produced changes in dopamine‐dependent behaviors including those associated with schizophrenia (Lalive & Lüscher, 2016). Coupled to this, evidence for abnormalities in striatal GABA function impinging on dopamine transmission in schizophrenia, provides a plausible mechanism for the type of dysregulation of input to dopamine systems discussed by Howes and Kapur as a cause of schizophrenia (Howes & Kapur, 2009, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…They synapse not only onto other interneurons but also with both efferent and afferent neurons within the striatum making them well placed to regulate striatal function (Gittis & Kreitzer, 2012; Gonzales & Smith, 2015; Ma & Leung, 2014). GABA, acting through both ionotropic GABA‐A and metabotropic GABA‐B receptors modulates mesostriatal dopamine function (Lalive & Lüscher, 2016). Actions at the level of the cell bodies in the midbrain influence activation within the pathways as a whole, but there is also evidence for local modulatory effects mediated at the terminals in both dorsal and ventral striatum including NAc (Brodnik et al., 2019; Lopes et al., 2019; Pitman et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

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Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub‐chronic phencyclidine pretreatment

Ferdinand

Peters

Yavas

et al. 2021

J of Neuroscience Research

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Dopamine signaling in nucleus accumbens (NAc) is modulated by γ‐aminobutyric acid (GABA), acting through GABA‐A and GABA‐B receptors: dysregulation of GABAergic control of dopamine function may be important in behavioral deficits in schizophrenia. We investigated the effect of GABA‐A (muscimol) and GABA‐B (baclofen) receptor agonists on electrically stimulated dopamine release. Furthermore, we explored whether drug‐induced changes were disrupted by pretreatment with phencyclidine, which provides a well‐validated model of schizophrenia. Using brain slices from female rats, fast‐scan cyclic voltammetry was used to measure electrically stimulated dopamine release in NAc shell. Both muscimol and baclofen caused concentration‐dependent attenuation of evoked dopamine release: neither effect was changed by dihydro‐β‐erythroidine, a nicotinic acetylcholine receptor antagonist, or the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)‐type glutamate receptor antagonist, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), precluding indirect mechanisms using these transmitter systems in the GABAergic actions. In slices taken from rats pretreated with phencyclidine, the attenuation of evoked dopamine release by baclofen was abolished, but the attenuation by muscimol was unaffected. Since phencyclidine pretreatment was followed by drug‐free washout period of at least a week, the drug was not present during recording. Therefore, disruption of GABA‐B modulation of dopamine is due to long‐term functional changes resulting from the treatment, rather than transient changes due to the drug's presence at test. This enduring dysregulation of GABA‐B modulation of accumbal dopamine release provides a plausible mechanism through which GABA dysfunction influences accumbal dopamine leading to behavioral changes seen in schizophrenia and may provide a route for novel therapeutic strategies to treat the condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub‐chronic phencyclidine pretreatment

Ferdinand

Peters

Yavas

et al. 2021

J of Neuroscience Research

View full text Add to dashboard Cite

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“…GABA B receptors are well expressed in the mesocorticolimbic dopamine system, where they control neuronal activity and the release of GABA, glutamate and dopamine ( Lalive and Lüscher, 2016 ). Accordingly, pharmacological activation of GABA B receptors by the selective agonist baclofen reduced several addictive behaviors in preclinical studies such as the development and expression of psychostimulant-induced motor sensitization ( Bartoletti et al, 2004 , 2005 ; Cedillo et al, 2019 ), drug seeking ( Li et al, 2001 ), drug self-administration ( Roberts and Brebner, 2000 ; Ranaldi and Poeggel, 2002 ; Brebner et al, 2005 ) and drug-induced cognitive impairment ( Arai et al, 2009 ; Mizoguchi and Yamada, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Restoring GABAB receptor expression in the ventral tegmental area of methamphetamine addicted mice inhibits locomotor sensitization and drug seeking behavior

Hleihil,

Benke

2024

Front. Mol. Neurosci.

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Repeated exposure to psychostimulants such as methamphetamine (METH) induces neuronal adaptations in the mesocorticolimbic dopamine system, including the ventral tegmental area (VTA). These changes lead to persistently enhanced neuronal activity causing increased dopamine release and addictive phenotypes. A factor contributing to increased dopaminergic activity in this system appears to be reduced GABAB receptor-mediated neuronal inhibition in the VTA. Dephosphorylation of serine 783 (Ser783) of the GABAB2 subunit by protein phosphatase 2A (PP2A) appears to trigger the downregulation GABAB receptors in psychostimulant-addicted rodents. Therefore, preventing the interaction of GABAB receptors with PP2A using an interfering peptide is a promising strategy to restore GABAB receptor-mediated neuronal inhibition. We have previously developed an interfering peptide (PP2A-Pep) that inhibits the GABAB receptors/PP2A interaction and thereby restores receptor expression under pathological conditions. Here, we tested the hypothesis that restoration of GABAB receptor expression in the VTA of METH addicted mice reduce addictive phenotypes. We found that the expression of GABAB receptors was significantly reduced in the VTA and nucleus accumbens but not in the hippocampus and somatosensory cortex of METH-addicted mice. Infusion of PP2A-Pep into the VTA of METH-addicted mice restored GABAB receptor expression in the VTA and inhibited METH-induced locomotor sensitization as assessed in the open field test. Moreover, administration of PP2A-Pep into the VTA also reduced drug seeking behavior in the conditioned place preference test. These observations underscore the importance of VTA GABAB receptors in controlling addictive phenotypes. Furthermore, this study illustrates the value of interfering peptides targeting diseases-related protein-protein interactions as an alternative approach for a potential development of selective therapeutic interventions.

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GABAB Receptors and Drug Addiction: Psychostimulants and Other Drugs of Abuse

Slesinger

2020

Current Topics in Behavioral Neurosciences

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GABAB Receptor Functions in the Mesolimbic Dopamine System

Cited by 8 publications

References 117 publications

Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub‐chronic phencyclidine pretreatment

Modulation of stimulated dopamine release in rat nucleus accumbens shell by GABA in vitro: Effect of sub‐chronic phencyclidine pretreatment

Restoring GABAB receptor expression in the ventral tegmental area of methamphetamine addicted mice inhibits locomotor sensitization and drug seeking behavior

GABAB Receptors and Drug Addiction: Psychostimulants and Other Drugs of Abuse

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