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α7 nicotinic acetylcholine receptor modulation of accumbal dopamine release covaries with novelty seeking.

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Title: α7 nicotinic acetylcholine receptor modulation of accumbal dopamine release covaries with novelty seeking.
Authors: Leach, Amy C. (AUTHOR), Pitts, Elizabeth G. (AUTHOR), Siciliano, Cody A. (AUTHOR), Ferris, Mark J. (AUTHOR)
Source: European Journal of Neuroscience. Mar2022, Vol. 55 Issue 5, p1162-1173. 12p. 4 Graphs.
Subjects: Nicotinic acetylcholine receptors, Dopamine, Nucleus accumbens, Methyl aspartate receptors
Abstract: Heightened novelty‐seeking phenotypes are associated with a range of behavioural traits including susceptibility to drug use. These relationships are recapitulated in preclinical models, where rats that exhibit increased exploratory activity in novel environments (high responders—HR) acquire self‐administration of psychostimulants more rapidly compared to rats that display low novelty exploration (low responders—LR). Dopamine release dynamics in the nucleus accumbens (NAc) covaries with response to novelty, and differences in dopaminergic signalling are thought to be a major underlying driver of the link between novelty seeking and drug use vulnerability. Accumbal dopamine release is controlled by local microcircuits including modulation through glutamatergic and nicotinic acetylcholine receptor (nAChR) systems, but whether these mechanisms contribute to disparate dopamine signalling across novelty phenotypes is unclear. Here, we used ex vivo voltammetry in the NAc of rats to determine if α7 nAChRs contribute to differential dopamine dynamics associated with individual differences in novelty exploration. We found that blockade of α7 nAChRs attenuates tonic dopamine release evoked by low‐frequency stimulations across phenotypes but that phasic release is decreased in LRs while HRs are unaffected. These stimulation frequency‐ and phenotype‐dependent effects result in a decreased dynamic range of release exclusively in LRs. Furthermore, we found that differential α7 modulation of dopamine release in LRs is dependent on AMPA but not NMDA receptors. These results help to form an understanding of the local NAc microcircuitry and provide a potential mechanism for covariance of dopamine dynamics and sensitivity to the reinforcing effects of drugs of abuse. [ABSTRACT FROM AUTHOR]
Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Label: Title
  Group: Ti
  Data: α7 nicotinic acetylcholine receptor modulation of accumbal dopamine release covaries with novelty seeking.
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  Data: <searchLink fieldCode="AR" term="%22Leach%2C+Amy+C%2E%22">Leach, Amy C.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Pitts%2C+Elizabeth+G%2E%22">Pitts, Elizabeth G.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Siciliano%2C+Cody+A%2E%22">Siciliano, Cody A.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ferris%2C+Mark+J%2E%22">Ferris, Mark J.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Journal+of+Neuroscience%22">European Journal of Neuroscience</searchLink>. Mar2022, Vol. 55 Issue 5, p1162-1173. 12p. 4 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Nicotinic+acetylcholine+receptors%22">Nicotinic acetylcholine receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Dopamine%22">Dopamine</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleus+accumbens%22">Nucleus accumbens</searchLink><br /><searchLink fieldCode="DE" term="%22Methyl+aspartate+receptors%22">Methyl aspartate receptors</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Heightened novelty‐seeking phenotypes are associated with a range of behavioural traits including susceptibility to drug use. These relationships are recapitulated in preclinical models, where rats that exhibit increased exploratory activity in novel environments (high responders—HR) acquire self‐administration of psychostimulants more rapidly compared to rats that display low novelty exploration (low responders—LR). Dopamine release dynamics in the nucleus accumbens (NAc) covaries with response to novelty, and differences in dopaminergic signalling are thought to be a major underlying driver of the link between novelty seeking and drug use vulnerability. Accumbal dopamine release is controlled by local microcircuits including modulation through glutamatergic and nicotinic acetylcholine receptor (nAChR) systems, but whether these mechanisms contribute to disparate dopamine signalling across novelty phenotypes is unclear. Here, we used ex vivo voltammetry in the NAc of rats to determine if α7 nAChRs contribute to differential dopamine dynamics associated with individual differences in novelty exploration. We found that blockade of α7 nAChRs attenuates tonic dopamine release evoked by low‐frequency stimulations across phenotypes but that phasic release is decreased in LRs while HRs are unaffected. These stimulation frequency‐ and phenotype‐dependent effects result in a decreased dynamic range of release exclusively in LRs. Furthermore, we found that differential α7 modulation of dopamine release in LRs is dependent on AMPA but not NMDA receptors. These results help to form an understanding of the local NAc microcircuitry and provide a potential mechanism for covariance of dopamine dynamics and sensitivity to the reinforcing effects of drugs of abuse. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of European Journal of Neuroscience is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/ejn.15620
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              Text: Mar2022
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