MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro
The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the express...
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PeerJ Inc.
2013-04-01
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| Online Access: | https://peerj.com/articles/61.pdf |
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| author | F Woodward Hopf Taban Seif Shinjae Chung Olivier Civelli |
| author_facet | F Woodward Hopf Taban Seif Shinjae Chung Olivier Civelli |
| author_sort | F Woodward Hopf |
| collection | DOAJ |
| description | The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report (Chung et al., 2011a) showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell), a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition. |
| first_indexed | 2024-03-09T05:14:36Z |
| format | Article |
| id | doaj.art-01d777cb4d7a4c78bdd78f1e53d3dde5 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T05:14:36Z |
| publishDate | 2013-04-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-01d777cb4d7a4c78bdd78f1e53d3dde52023-12-03T12:46:25ZengPeerJ Inc.PeerJ2167-83592013-04-011e6110.7717/peerj.6161MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitroF Woodward Hopf0Taban Seif1Shinjae Chung2Olivier Civelli3Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, CA, USAErnest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, CA, USADepartment of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, USADepartments of Pharmacology and Developmental and Cell Biology, University of California, Irvine, CA, USAThe MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report (Chung et al., 2011a) showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell), a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition.https://peerj.com/articles/61.pdfSchizophreniaNucleus accumbens shellMCHDopamine receptorApomorphine |
| spellingShingle | F Woodward Hopf Taban Seif Shinjae Chung Olivier Civelli MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro PeerJ Schizophrenia Nucleus accumbens shell MCH Dopamine receptor Apomorphine |
| title | MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro |
| title_full | MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro |
| title_fullStr | MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro |
| title_full_unstemmed | MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro |
| title_short | MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro |
| title_sort | mch and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro |
| topic | Schizophrenia Nucleus accumbens shell MCH Dopamine receptor Apomorphine |
| url | https://peerj.com/articles/61.pdf |
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