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The glycine reuptake inhibitor org 25935 interacts with basal and ethanol-induced dopamine release in rat nucleus accumbens.
Alcohol Clin Exp Res. 2009 Jul; 33(7):1151-7.AC

Abstract

BACKGROUND

The mesolimbic dopamine (DA) projection from the ventral tegmental area to nucleus accumbens (nAc), a central part of the reward system, is activated by ethanol (EtOH) and other drugs of abuse. We have previously demonstrated that the glycine receptor in the nAc and its amino acid agonists may be implicated in the DA activation and reinforcing properties of EtOH. We have also reported that the glycine transporter 1 inhibitor, Org 25935, produces a robust and dose-dependent decrease in EtOH consumption in Wistar rats. The present study explores the interaction between EtOH and Org 25935 with respect to DA levels in the rat nAc.

METHODS

The effects of Org 25935 (6 mg/kg, i.p.) and/or EtOH (2.5 g/kg, i.p.) on accumbal DA levels were examined by means of in vivo microdialysis (coupled to HPLC-ED) in freely moving male Wistar rats. The effect of Org 25935 on accumbal glycine output was also investigated.

RESULTS

Systemic Org 25935 increased DA output in a subpopulation of rats (52% in Experiment 1 and 38% in Experiment 2). In Experiment 2, EtOH produced a significant increase in DA levels in vehicles (35%) and in Org 25935 nonresponders (19%), whereas EtOH did not further increase the DA level in rats responding to Org 25935 (2%). The same dose of Org 25935 increased glycine levels by 87% in nAc.

CONCLUSIONS

This study demonstrates that Org 25935, probably via increased glycine levels, (i) counteracts EtOH-induced increases of accumbal DA levels and (ii) increases basal DA levels in a subpopulation of rats. The results are in line with previous findings and it is suggested that the effects observed involve interference with accumbal GlyRs and are related to the alcohol consumption modulating effect of Org 25935.

Authors+Show Affiliations

Section of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg and Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden. helga.lido@neuro.gu.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19389199

Citation

Lidö, Helga Höifödt, et al. "The Glycine Reuptake Inhibitor Org 25935 Interacts With Basal and Ethanol-induced Dopamine Release in Rat Nucleus Accumbens." Alcoholism, Clinical and Experimental Research, vol. 33, no. 7, 2009, pp. 1151-7.
Lidö HH, Stomberg R, Fagerberg A, et al. The glycine reuptake inhibitor org 25935 interacts with basal and ethanol-induced dopamine release in rat nucleus accumbens. Alcohol Clin Exp Res. 2009;33(7):1151-7.
Lidö, H. H., Stomberg, R., Fagerberg, A., Ericson, M., & Söderpalm, B. (2009). The glycine reuptake inhibitor org 25935 interacts with basal and ethanol-induced dopamine release in rat nucleus accumbens. Alcoholism, Clinical and Experimental Research, 33(7), 1151-7. https://doi.org/10.1111/j.1530-0277.2009.00938.x
Lidö HH, et al. The Glycine Reuptake Inhibitor Org 25935 Interacts With Basal and Ethanol-induced Dopamine Release in Rat Nucleus Accumbens. Alcohol Clin Exp Res. 2009;33(7):1151-7. PubMed PMID: 19389199.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The glycine reuptake inhibitor org 25935 interacts with basal and ethanol-induced dopamine release in rat nucleus accumbens. AU - Lidö,Helga Höifödt, AU - Stomberg,Rosita, AU - Fagerberg,Anne, AU - Ericson,Mia, AU - Söderpalm,Bo, Y1 - 2009/04/09/ PY - 2009/4/25/entrez PY - 2009/4/25/pubmed PY - 2010/3/27/medline SP - 1151 EP - 7 JF - Alcoholism, clinical and experimental research JO - Alcohol Clin Exp Res VL - 33 IS - 7 N2 - BACKGROUND: The mesolimbic dopamine (DA) projection from the ventral tegmental area to nucleus accumbens (nAc), a central part of the reward system, is activated by ethanol (EtOH) and other drugs of abuse. We have previously demonstrated that the glycine receptor in the nAc and its amino acid agonists may be implicated in the DA activation and reinforcing properties of EtOH. We have also reported that the glycine transporter 1 inhibitor, Org 25935, produces a robust and dose-dependent decrease in EtOH consumption in Wistar rats. The present study explores the interaction between EtOH and Org 25935 with respect to DA levels in the rat nAc. METHODS: The effects of Org 25935 (6 mg/kg, i.p.) and/or EtOH (2.5 g/kg, i.p.) on accumbal DA levels were examined by means of in vivo microdialysis (coupled to HPLC-ED) in freely moving male Wistar rats. The effect of Org 25935 on accumbal glycine output was also investigated. RESULTS: Systemic Org 25935 increased DA output in a subpopulation of rats (52% in Experiment 1 and 38% in Experiment 2). In Experiment 2, EtOH produced a significant increase in DA levels in vehicles (35%) and in Org 25935 nonresponders (19%), whereas EtOH did not further increase the DA level in rats responding to Org 25935 (2%). The same dose of Org 25935 increased glycine levels by 87% in nAc. CONCLUSIONS: This study demonstrates that Org 25935, probably via increased glycine levels, (i) counteracts EtOH-induced increases of accumbal DA levels and (ii) increases basal DA levels in a subpopulation of rats. The results are in line with previous findings and it is suggested that the effects observed involve interference with accumbal GlyRs and are related to the alcohol consumption modulating effect of Org 25935. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/19389199/The_glycine_reuptake_inhibitor_org_25935_interacts_with_basal_and_ethanol_induced_dopamine_release_in_rat_nucleus_accumbens_ L2 - https://doi.org/10.1111/j.1530-0277.2009.00938.x DB - PRIME DP - Unbound Medicine ER -