Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective [version 1; referees: 2 approved]
Glutamate signaling in the brain is one of the most studied targets in the alcohol research field. Here, we report the current understanding of how the excitatory neurotransmitter glutamate, its receptors, and its transporters are involved in low, episodic, and heavy alcohol use. Specific animal beh...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
F1000 Research Ltd
2017-03-01
|
| Series: | F1000Research |
| Subjects: | |
| Online Access: | https://f1000research.com/articles/6-298/v1 |
| _version_ | 1819051893088845824 |
|---|---|
| author | Lara Hwa Joyce Besheer Thomas Kash |
| author_facet | Lara Hwa Joyce Besheer Thomas Kash |
| author_sort | Lara Hwa |
| collection | DOAJ |
| description | Glutamate signaling in the brain is one of the most studied targets in the alcohol research field. Here, we report the current understanding of how the excitatory neurotransmitter glutamate, its receptors, and its transporters are involved in low, episodic, and heavy alcohol use. Specific animal behavior protocols can be used to assess these different drinking levels, including two-bottle choice, operant self-administration, drinking in the dark, the alcohol deprivation effect, intermittent access to alcohol, and chronic intermittent ethanol vapor inhalation. Importantly, these methods are not limited to a specific category, since they can be interchanged to assess different states in the development from low to heavy drinking. We encourage a circuit-based perspective beyond the classic mesolimbic-centric view, as multiple structures are dynamically engaged during the transition from positive- to negative-related reinforcement to drive alcohol drinking. During this shift from lower-level alcohol drinking to heavy alcohol use, there appears to be a shift from metabotropic glutamate receptor-dependent behaviors to N-methyl-D-aspartate receptor-related processes. Despite high efficacy of the glutamate-related pharmaceutical acamprosate in animal models of drinking, it is ineffective as treatment in the clinic. Therefore, research needs to focus on other promising glutamatergic compounds to reduce heavy drinking or mediate withdrawal symptoms or both. |
| first_indexed | 2024-12-21T12:11:10Z |
| format | Article |
| id | doaj.art-7887f5f6a6b7487882c0421fc8e8699f |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-21T12:11:10Z |
| publishDate | 2017-03-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-7887f5f6a6b7487882c0421fc8e8699f2022-12-21T19:04:34ZengF1000 Research LtdF1000Research2046-14022017-03-01610.12688/f1000research.9609.110352Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective [version 1; referees: 2 approved]Lara Hwa0Joyce Besheer1Thomas Kash2Department of Pharmacology, University of North Carolina School of Medicine, Bowles Center for Alcohol Studies, Chapel Hill, NC, 27599, USADepartment of Psychiatry, University of North Carolina School of Medicine, Bowles Center for Alcohol Studies, Chapel Hill, NC, 27599, USADepartment of Pharmacology, University of North Carolina School of Medicine, Bowles Center for Alcohol Studies, Chapel Hill, NC, 27599, USAGlutamate signaling in the brain is one of the most studied targets in the alcohol research field. Here, we report the current understanding of how the excitatory neurotransmitter glutamate, its receptors, and its transporters are involved in low, episodic, and heavy alcohol use. Specific animal behavior protocols can be used to assess these different drinking levels, including two-bottle choice, operant self-administration, drinking in the dark, the alcohol deprivation effect, intermittent access to alcohol, and chronic intermittent ethanol vapor inhalation. Importantly, these methods are not limited to a specific category, since they can be interchanged to assess different states in the development from low to heavy drinking. We encourage a circuit-based perspective beyond the classic mesolimbic-centric view, as multiple structures are dynamically engaged during the transition from positive- to negative-related reinforcement to drive alcohol drinking. During this shift from lower-level alcohol drinking to heavy alcohol use, there appears to be a shift from metabotropic glutamate receptor-dependent behaviors to N-methyl-D-aspartate receptor-related processes. Despite high efficacy of the glutamate-related pharmaceutical acamprosate in animal models of drinking, it is ineffective as treatment in the clinic. Therefore, research needs to focus on other promising glutamatergic compounds to reduce heavy drinking or mediate withdrawal symptoms or both.https://f1000research.com/articles/6-298/v1Behavioral NeuroscienceMedical GeneticsNeurobiology of Disease & RegenerationNeuronal Signaling MechanismsNeuropharmacology & Psychopharmacology |
| spellingShingle | Lara Hwa Joyce Besheer Thomas Kash Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective [version 1; referees: 2 approved] F1000Research Behavioral Neuroscience Medical Genetics Neurobiology of Disease & Regeneration Neuronal Signaling Mechanisms Neuropharmacology & Psychopharmacology |
| title | Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective [version 1; referees: 2 approved] |
| title_full | Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective [version 1; referees: 2 approved] |
| title_fullStr | Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective [version 1; referees: 2 approved] |
| title_full_unstemmed | Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective [version 1; referees: 2 approved] |
| title_short | Glutamate plasticity woven through the progression to alcohol use disorder: a multi-circuit perspective [version 1; referees: 2 approved] |
| title_sort | glutamate plasticity woven through the progression to alcohol use disorder a multi circuit perspective version 1 referees 2 approved |
| topic | Behavioral Neuroscience Medical Genetics Neurobiology of Disease & Regeneration Neuronal Signaling Mechanisms Neuropharmacology & Psychopharmacology |
| url | https://f1000research.com/articles/6-298/v1 |
| work_keys_str_mv | AT larahwa glutamateplasticitywoventhroughtheprogressiontoalcoholusedisorderamulticircuitperspectiveversion1referees2approved AT joycebesheer glutamateplasticitywoventhroughtheprogressiontoalcoholusedisorderamulticircuitperspectiveversion1referees2approved AT thomaskash glutamateplasticitywoventhroughtheprogressiontoalcoholusedisorderamulticircuitperspectiveversion1referees2approved |