A unique multi-synaptic mechanism involving acetylcholine and GABA regulates dopamine release in the nucleus accumbens through early adolescence in male rats
- Wake Forest University, United States
- University of Kentucky, United States
Abstract
Adolescence is characterized by changes in reward-related behaviors, social behaviors, and decision making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the associated behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry and microdialysis to examine differences in dopamine release as well as mechanisms that underlie differential dopamine signaling in the nucleus accumbens (NAc) core of adolescent (P28-35) and adult (P70-90) male rats. We show baseline differences between adult and adolescent stimulated dopamine release in male rats, as well as opposite effects of the a6 nicotinic acetylcholine receptor (nAChR) on modulating dopamine release. The a6-selective blocker, a-conotoxin, increased dopamine release in early adolescent rats, but decreased dopamine release in rats beginning in middle adolescence and extending through adulthood. Strikingly, blockade of GABAA and GABAB receptors revealed that this a6-mediated increase in adolescent dopamine release requires NAc GABA signaling to occur. We confirm the role of a6 nAChR and GABA in mediating this effect in vivo using microdialysis. Results herein suggest a multisynaptic mechanism potentially unique to the period of development that includes early adolescence, involving acetylcholine acting at a6-containing nAChRs to drive inhibitory GABA tone on dopamine release.
Data availability
All data generated or analyzed for this study are available at Harvard dataverse (https://dataverse.harvard.edu/) under the title eLife_2024_Iacino_Ferris, or through the following link:https://doi.org/10.7910/DVN/8D2FJ0
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eLife_2024_Iacino_FerrisHarvard Dataverse https://doi.org/10.7910/DVN/8D2FJ0.
Article and author information
Author details
Funding
National Institute on Drug Abuse (DA031791)
- Mark J Ferris
National Institute on Drug Abuse (DA006634)
- Mark J Ferris
National Institute on Alcohol Abuse and Alcoholism (AA026117)
- Mark J Ferris
National Institute on Alcohol Abuse and Alcoholism (AA028162)
- Elizabeth G Pitts
National Institute of General Medical Sciences (GM102773)
- Elizabeth G Pitts
Peter McManus Charitable Trust
- Mark J Ferris
National Institute on Drug Abuse (DA058517)
- Melody C Iacino
National Institute on Drug Abuse (DA052460)
- Mark J Ferris
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animals were maintained according to the National Institutes of Health guidelines in Association for Assessment and Accreditation of Laboratory Animal Care accredited facilities (Accreditation #: 00008; PHS Assurance #: D16-00248 (A3391-01)). All experimental protocols were approved by the Institutional Animal Care and Use Committee at Wake Forest School of Medicine (Protocol Approval #: A21-143).
Copyright
© 2024, Iacino et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A unique multi-synaptic mechanism involving acetylcholine and GABA regulates dopamine release in the nucleus accumbens through early adolescence in male rats
eLife 13:e62999.
https://doi.org/10.7554/eLife.62999
