Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex
Abstract
It has previously been shown that inescapable (IS) but not escapable (ES) stress potentiates the rewarding properties of morphine as measured by conditioned place preference and psychomotor activation, and that this potentiation may be mediated by dorsal raphe nucleus (DRN) serotonin (5-HT) neurons. The medial prefrontal cortex (mPFC) has been implicated in both reward and stress, and is a projection region of the DRN. The mPFC also contains dopaminergic afferents from the ventral tegmental area, which has been the focus of many studies exploring both the rewarding properties of drugs and the aversive properties of stress. The role of the mPFC in stress/drug reactivity interactions is largely unknown. The present study used in vivo microdialysis to examine 5-HT and dopamine (DA) efflux in the mPFC of rats during IS, ES or no stress (NS). IS and ES rats received the stressor in yoked pairs. The stressor consisted of tailshocks that could be terminated for both rats by the ES rats. Large increases in 5-HT and DA levels were observed during IS but not ES or NS. DA and 5-HT efflux were also measured 24 h later in the same rats in response to morphine (3 mg/kg) or saline. Sustained increases in 5-HT levels were observed after morphine in rats that had previously received IS but not in rats that had received ES or NS. No changes in DA efflux were observed after morphine. Thus, 5-HT and DA in the mPFC may be involved in stressor controllability effects, and the sensitization of 5-HT neurons by IS extends to the mPFC and to morphine as a challenge.
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Serotonin is released in the PFC during exposure to uncontrollable stress and is key to orbital PFC function.
“For example, important work is underway to reveal the complex and powerful effects on prefrontal functions of serotonin, another modulator that is released in the PFC during exposure to uncontrollable stress158 and that is key to orbital PFC function159.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [158]
Following uncontrollable stressors, increased reliance on the spectator relative to the actor model probably involves several other brain areas, including the mPFC and the dorsal raphe nucleus.
“Yet, this increased reliance on the spectator relative to the actor model following uncontrollable stressors probably involves several other brain areas, including the mPFC and the dorsal raphe nucleus, both of which are highly sensitive to stressor controllability [14][15][16] .”
From Stress-sensitive inference of task controllability (2022) · cites this paper as [15]
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- Authors
- Bland, S. T., Hargrave, D., Pepin, J. L., Amat, J., Watkins, L. R., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Bland, Sondra T
- Venue
- Neuropsychopharmacology
- Published
- 2003-03-21
- Volume
- 28
- Issue
- 9
- Pages
- 1589-1596
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2073082215
- Cited by
- 155
- References
- 61
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 9 · 2012: 6
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (MH 50479)
- National Institute of Mental Health (MH 50479)
- National Institute on Drug Abuse (R01DA013159, DA 13159)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- stressor controllability, inescapable stress, serotonin release, morphine, medial prefrontal cortex, dorsal raphe nucleus, tail shock, conditioned place preference
- MeSH terms
- Animals, Behavior, Animal, Chromatography, High Pressure Liquid, Conditioning, Psychological, Dopamine, Electroshock, Male, Morphine, Narcotics, Psychomotor Performance, Serotonin, Stress, Physiological, Time Factors, Rats, Sprague-Dawley, Prefrontal Cortex, Microdialysis, Rats
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