Involvement of Inhibitory Receptors in Modulating Dopamine Signaling and Synaptic Activity Following Acute Ethanol Exposure in Striatal Subregions

Clarke, Rhona B. C.; Söderpalm, Bo; Lotfi, Amin; Ericson, Mia; Adermark, Louise

doi:10.1111/acer.12895

Cited by 17 publications

(13 citation statements)

References 58 publications

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“…, ; Clarke et al . ). Finally, the presence of GlyRs in D1 MSN (Kravitz & Kreitzer, ) suggests an important role of these receptors in the activation of the direct pathway between VTA and nAc (Koob & Nestler, ), possibly by neuronal disinhibition.…”

Section: Discussionmentioning

confidence: 97%

Presence of ethanol‐sensitive glycine receptors in medium spiny neurons in the mouse nucleus accumbens

Förstera

Muñoz

Lobo

et al. 2017

The Journal of Physiology

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Alcohol abuse causes major social, economic and health-related problems worldwide. Alcohol, like other drugs of abuse, increases levels of dopamine in the nucleus accumbens (nAc), facilitating behavioural reinforcement and substance abuse. Previous studies suggested that glycine receptors (GlyRs) are involved in the regulation of accumbal dopamine levels. Here, we investigated the presence of GlyRs in accumbal dopamine receptor medium spiny neurons (MSNs) of C57BL/6J mice, analysing mRNA expression levels and immunoreactivity of GlyR subunits, as well as ethanol sensitivity. We found that GlyR α1 subunits are expressed at higher levels than α2, α3 and β in the mouse nAc and were located preferentially in dopamine receptor 1 (DRD1)-positive MSNs. Interestingly, the glycine-evoked currents in dissociated DRD1-positive MSNs were potentiated by ethanol. Also, the potentiation of the GlyR-mediated tonic current by ethanol suggests that they modulate the excitability of DRD1-positive MSNs in nAc. This study should contribute to understanding the role of GlyR α1 in the reward system and might help to develop novel pharmacological therapies to treat alcoholism and other addiction-related and compulsive behaviours.

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Section: Discussionmentioning

confidence: 97%

Presence of ethanol‐sensitive glycine receptors in medium spiny neurons in the mouse nucleus accumbens

Förstera

Muñoz

Lobo

et al. 2017

The Journal of Physiology

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“…In vivo microdialysis was performed in the nAc, DMS, and DLS of awake and freely moving Wistar rats (250–350 g) as described previously (Adermark et al , 2015; Clarke et al , 2015). In brief, rats were implanted with an I-shaped custom-made dialysis probe into the nAc (coordinates: AP: +1.85 mm; ML: −1.4 mm relative to bregma; DV: −7.8 mm relative to brain surface), DMS (+1.2, −2.0, −5.5) or DLS (+1.2, −3.5, −5.5).…”

Section: Methodsmentioning

confidence: 99%

Temporal Rewiring of Striatal Circuits Initiated by Nicotine

Adermark

Morud

Lotfi

et al. 2016

Neuropsychopharmacol

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Drug addiction has been conceptualized as maladaptive recruitment of integrative circuits coursing through the striatum, facilitating drug-seeking and drug-taking behavior. The aim of this study was to define temporal neuroadaptations in striatal subregions initiated by 3 weeks of intermittent nicotine exposure followed by protracted abstinence. Enhanced rearing activity was assessed in motor activity boxes as a measurement of behavioral change induced by nicotine (0.36 mg/kg), whereas electrophysiological field potential recordings were performed to evaluate treatment effects on neuronal activity. Dopamine receptor mRNA expression was quantified by qPCR, and nicotine-induced dopamine release was measured in striatal subregions using in vivo microdialysis. Golgi staining was performed to assess nicotine-induced changes in spine density of medium spiny neurons. The data presented here show that a brief period of nicotine exposure followed by abstinence leads to temporal changes in synaptic efficacy, dopamine receptor expression, and spine density in a subregion-specific manner. Nicotine may thus initiate a reorganization of striatal circuits that continues to develop despite protracted abstinence. We also show that the response to nicotine is modulated in previously exposed rats even after 6 months of abstinence. The data presented here suggests that, even though not self-administered, nicotine may produce progressive neuronal alterations in brain regions associated with goal-directed and habitual performance, which might contribute to the development of compulsive drug seeking and the increased vulnerability to relapse, which are hallmarks of drug addiction.

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“…On a general note, both taurine and EtOH can increase the flow of chloride ions by direct or allosteric activation of GABA A or GlyRs (Bureau and Olsen, ; Engblom and Akerman, ; Okamoto and Sakai, ; Ticku, ) and inhibit glutamatergic transmission at NMDA receptors (Chan et al., ; Wright et al., ). However, the similarities between EtOH and taurine appear to be region specific (Clarke et al., ; Ulenius et al., ) indicating a complexity in need of detailed studies. In addition, EtOH increases extracellular taurine levels in the nAc and in other brain regions (Dahchour et al., , ; Quertemont et al., ; Smith et al., ), and perfusion of taurine in nAc by reversed microdialysis increases DA levels in the same region via mechanisms similar to those of EtOH (Ericson et al., , ).…”

Section: Taurine and Other Amino Acid Ligands For The Glyrmentioning

confidence: 99%

The Glycine Receptor—A Functionally Important Primary Brain Target of Ethanol

Söderpalm

Lidö

Ericson

2017

Alcoholism Clin & Exp Res

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Identification of ethanol's (EtOH) primary molecular brain targets and determination of their functional role is an ongoing, important quest. Pentameric ligand-gated ion channels, that is, the nicotinic acetylcholine receptor, the γ-aminobutyric acid type A receptor, the 5-hydroxytryptamine , and the glycine receptor (GlyR), are such targets. Here, aspects of the structure and function of these receptors and EtOH's interaction with them are briefly reviewed, with special emphasis on the GlyR and the importance of this receptor and its ligands for EtOH pharmacology. It is suggested that GlyRs are involved in (i) the dopamine-activating effect of EtOH, (ii) regulating EtOH intake, and (iii) the relapse preventing effect of acamprosate. Exploration of the GlyR subtypes involved and efforts to develop subtype specific agonists or antagonists may offer new pharmacotherapies for alcohol use disorders.

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Involvement of Inhibitory Receptors in Modulating Dopamine Signaling and Synaptic Activity Following Acute Ethanol Exposure in Striatal Subregions

Abstract: The current results show that changes in striatal dopamine output and synaptic activity induced by acute EtOH administration are modulated by inhibitory receptors in a subregion-specific manner.

Cited by 17 publications

References 58 publications

Presence of ethanol‐sensitive glycine receptors in medium spiny neurons in the mouse nucleus accumbens

Presence of ethanol‐sensitive glycine receptors in medium spiny neurons in the mouse nucleus accumbens

Temporal Rewiring of Striatal Circuits Initiated by Nicotine

The Glycine Receptor—A Functionally Important Primary Brain Target of Ethanol

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