Increased dopamine and norepinephrine release in medial prefrontal cortex induced by acute and chronic stress: effects of diazepam
Abstract
We have examined the effects of diazepam on the stress-induced increase in extracellular dopamine and norepinephrine in the medial prefrontal cortex using in vivo microdialysis. In naive rats, acute tail pressure (30 min) elicited an increase in the concentrations of dopamine and norepinephrine in extracellular fluid of medial prefrontal cortex (+54 and +50%, respectively). Diazepam (2.5 mg/kg, i.p.) decreased the basal concentration of extracellular dopamine and norepinephrine. Diazepam also attenuated the stress-evoked increase in the absolute concentrations of extracellular dopamine (+17%), but did not alter the stress-induced increase in norepinephrine (+41%). However, when the drug-induced decrease in basal dopamine and norepinephrine concentration was taken into account, the stress-induced net increase in dopamine above the new baseline was equivalent to that obtained in vehicle pretreated rats, whereas the net increase in norepinephrine was almost twice that obtained in control subjects. In rats previously exposed to chronic cold (three to four weeks at 5 degrees C), tail pressure again produced an increase in the concentrations of dopamine and norepinephrine in the medial prefrontal cortex (+42% and +92%, respectively). However, in these chronically stressed rats, diazepam no longer decreased basal dopamine or norepinephrine in extracellular fluid, nor did it affect the stress-induced increase in the concentrations of these catecholamines. These data indicate that diazepam has complex effects on the extracellular concentrations of dopamine and norepinephrine which vary depending upon whether the rat is undisturbed or stressed during the period of drug exposure as well as the rat's prior history of exposure to stress. Moreover, these data raise questions regarding the role of catecholamines in the mechanism by which diazepam exerts its anxiolytic properties.
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Under stressful conditions, there are high levels of catecholamine release in the PFC.
“Under stressful conditions, there are high levels of catecholamine release in PFC (Deutch and Roth, 1990; Finlay et al., 1995)”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Finlay et al., 1995
Both dopamine and norepinephrine release are increased in the medial PFC during acute stress exposure in rats.
“Biochemical studies in rats have consistently shown that both DA and NA release are increased in the medial PFC during acute stress exposure (30–32).”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [32]
Under conditions of uncontrollable stress, high levels of NE and DA release in PFC engage α1-AR and D1R to drive Ca2+-PKC and cAMP-PKA signaling, rapidly opening nearby K+ channels to weaken PFC network connectivity and impair working memory and top-down control.
“However, under conditions of uncontrollable stress, there are high levels of NE and DA release in the PFC (Finlay et al., 1995, Murphy et al., 1996), which engage α1-AR and D1R to drive Ca2+-PKC and cAMP-PKA signaling, rapidly opening nearby K+ channels to weaken PFC network connectivity and impair working memory and top-down control (Fig. 4B); (Arnsten et al., 2019, Birnbaum et al., 2004, Gamo et”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Finlay et al., 1995
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- Authors
- Finlay, J. M., Zigmond, M. J., & Abercrombie, E. D.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Finlay, J.M.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 1995-02
- Volume
- 64
- Issue
- 3
- Pages
- 619-628
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2033146497
- Cited by
- 434
- References
- 63
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 10 · 2023: 17 · 2022: 8 · 2021: 12 · 2020: 10 · 2019: 17 · 2018: 16 · 2017: 17 · 2016: 16 · 2015: 15 · 2014: 22 · 2013: 15 · 2012: 16
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- National Institutes of Health (5r01mh043947-02)
- National Institute of Mental Health (MH 43947, MH 45156, MH 00058, P50MH045156)
- 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 › Neuroscience and Neuropharmacology Research
- Keywords
- diazepam, acute stress, chronic stress, medial prefrontal cortex, dopamine, norepinephrine, anxiolytic mechanism, cold stress
- MeSH terms
- Animals, Cold Temperature, Diazepam, Dopamine, Dose-Response Relationship, Drug, Homovanillic Acid, Male, Norepinephrine, Nucleus Accumbens, Receptors, GABA-A, Stress, Physiological, Time Factors, 3,4-Dihydroxyphenylacetic Acid, Rats, Sprague-Dawley, Prefrontal Cortex, Microdialysis, Rats
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