Cargando…
Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours
Reward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodula...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782948/ https://www.ncbi.nlm.nih.gov/pubmed/34663867 http://dx.doi.org/10.1038/s41386-021-01196-y |
_version_ | 1784638420144881664 |
---|---|
author | Thomas, Catherine S. Mohammadkhani, Aida Rana, Madiha Qiao, Min Baimel, Corey Borgland, Stephanie L. |
author_facet | Thomas, Catherine S. Mohammadkhani, Aida Rana, Madiha Qiao, Min Baimel, Corey Borgland, Stephanie L. |
author_sort | Thomas, Catherine S. |
collection | PubMed |
description | Reward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodulatory factors, including input from lateral hypothalamic (LH) orexin/hypocretin neurons which also express and co-release the neuropeptide, dynorphin. Dynorphin in the VTA induces aversive conditioning through the Kappa opioid receptor (KOR) and decreases dopamine when administered intra-VTA. Exogenous application of orexin or orexin 1 receptor (oxR1) antagonists in the VTA bidirectionally modulates dopamine-driven motivation and reward-seeking behaviours, including the attribution of motivational value to primary rewards and associated conditioned stimuli. However, the effect of endogenous stimulation of LH orexin/dynorphin-containing projections to the VTA and the potential contribution of co-released dynorphin on mesolimbic dopamine and reward related processes remains uncharacterised. We combined optogenetic, electrochemical, and behavioural approaches to examine this. We found that optical stimulation of LH orexin/dynorphin inputs in the VTA potentiates mesolimbic dopamine neurotransmission in the nucleus accumbens (NAc) core, produces real time and conditioned place preference, and increases the food cue-directed orientation in a Pavlovian conditioning procedure. LH orexin/dynorphin potentiation of NAc dopamine release and real time place preference was blocked by an oxR1, but not KOR antagonist. Thus, rewarding effects associated with optical stimulation of LH orexin/dynorphin inputs in the VTA are predominantly driven by orexin rather than dynorphin. |
format | Online Article Text |
id | pubmed-8782948 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-87829482022-02-04 Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours Thomas, Catherine S. Mohammadkhani, Aida Rana, Madiha Qiao, Min Baimel, Corey Borgland, Stephanie L. Neuropsychopharmacology Article Reward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodulatory factors, including input from lateral hypothalamic (LH) orexin/hypocretin neurons which also express and co-release the neuropeptide, dynorphin. Dynorphin in the VTA induces aversive conditioning through the Kappa opioid receptor (KOR) and decreases dopamine when administered intra-VTA. Exogenous application of orexin or orexin 1 receptor (oxR1) antagonists in the VTA bidirectionally modulates dopamine-driven motivation and reward-seeking behaviours, including the attribution of motivational value to primary rewards and associated conditioned stimuli. However, the effect of endogenous stimulation of LH orexin/dynorphin-containing projections to the VTA and the potential contribution of co-released dynorphin on mesolimbic dopamine and reward related processes remains uncharacterised. We combined optogenetic, electrochemical, and behavioural approaches to examine this. We found that optical stimulation of LH orexin/dynorphin inputs in the VTA potentiates mesolimbic dopamine neurotransmission in the nucleus accumbens (NAc) core, produces real time and conditioned place preference, and increases the food cue-directed orientation in a Pavlovian conditioning procedure. LH orexin/dynorphin potentiation of NAc dopamine release and real time place preference was blocked by an oxR1, but not KOR antagonist. Thus, rewarding effects associated with optical stimulation of LH orexin/dynorphin inputs in the VTA are predominantly driven by orexin rather than dynorphin. Springer International Publishing 2021-10-18 2022-02 /pmc/articles/PMC8782948/ /pubmed/34663867 http://dx.doi.org/10.1038/s41386-021-01196-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Thomas, Catherine S. Mohammadkhani, Aida Rana, Madiha Qiao, Min Baimel, Corey Borgland, Stephanie L. Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours |
title | Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours |
title_full | Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours |
title_fullStr | Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours |
title_full_unstemmed | Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours |
title_short | Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours |
title_sort | optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782948/ https://www.ncbi.nlm.nih.gov/pubmed/34663867 http://dx.doi.org/10.1038/s41386-021-01196-y |
work_keys_str_mv | AT thomascatherines optogeneticstimulationoflateralhypothalamicorexindynorphininputsintheventraltegmentalareapotentiatesmesolimbicdopamineneurotransmissionandpromotesrewardseekingbehaviours AT mohammadkhaniaida optogeneticstimulationoflateralhypothalamicorexindynorphininputsintheventraltegmentalareapotentiatesmesolimbicdopamineneurotransmissionandpromotesrewardseekingbehaviours AT ranamadiha optogeneticstimulationoflateralhypothalamicorexindynorphininputsintheventraltegmentalareapotentiatesmesolimbicdopamineneurotransmissionandpromotesrewardseekingbehaviours AT qiaomin optogeneticstimulationoflateralhypothalamicorexindynorphininputsintheventraltegmentalareapotentiatesmesolimbicdopamineneurotransmissionandpromotesrewardseekingbehaviours AT baimelcorey optogeneticstimulationoflateralhypothalamicorexindynorphininputsintheventraltegmentalareapotentiatesmesolimbicdopamineneurotransmissionandpromotesrewardseekingbehaviours AT borglandstephaniel optogeneticstimulationoflateralhypothalamicorexindynorphininputsintheventraltegmentalareapotentiatesmesolimbicdopamineneurotransmissionandpromotesrewardseekingbehaviours |