Table 1.
Studies of the effects of stress/glucocorticoids on dopamine neurotransmission
| Experimental paradigm | Species (strain), gender | Age range at time of intervention | Type of intervention | Age at time of assay | Brain region(s) | Finding(s) [after stress/intervention, relative to controls] | Reference(s) |
|---|---|---|---|---|---|---|---|
| Studies in adolescents | |||||||
| Postmortem brain analysis after chronic stress | Rat (SD), M/F | PND35–40 | Chronic stress: 5-day social defeat | PND63 |
mPFC Striatum |
Decreased basal dopamine Increased DAT binding Increased DR1 binding |
Novick et al. (2011) |
| Postmortem brain analysis after chronic stress | Rat (SD), M/F | PND35–40 | Chronic stress: 5-day social defeat | PND63 | mPFC | Decreased basal dopamine | Watt et al. (2009) |
| Behavior and postmortem brain analysis after chronic stress | Rat (Long-Evans ), M/F | PND40–48 | Chronic stress: 5-day intermittent exposure to predator odor | PND62 |
PFC Behavior |
Decreased DR2 protein Hyperactivity in open field (anxiety-like) |
Wright et al. (2008) |
| Postmortem brain analysis after chronic stress plus amphetamine | Rat (SD), M/F | PND35–40 | Chronic stress: 5-day social defeat | PND63 |
mPFC Striatum |
Decreased basal dopamine Increased DAT binding Increased DR1 binding |
Burke et al. (2010, 2011, 2013) |
| Behavior and postmortem brain analysis after chronic stress | Rat (Wistar Han), M/F | PND28–42 | Chronic stress: 7-day intermittent predator odor and aversive environment | PND104–125 |
mPFC Behavior |
Increased MAOA gene expression Increased MAOA promoter histone H3 acetylation Increased aggression |
Marquez et al. (2013) |
| Behavior and electrophysiology after chronic stress | Rat (Long-Evans), M/F | PND28–77 | Chronic stress: 6-week social isolation | Immediately after chronic stress (PND77) |
NAc Behavior |
Increased electrically induced dopamine release and uptake Decreased time on open arm in elevated plus maze |
Yorgason et al. (2013) |
| Electrophysiology, behavior, and postmortem brain analysis after chronic stress | DISC1 (dominant-negative) mutant mouse, M/F | PND21–56 | Chronic stress: 3-week isolation stress | Immediately after chronic stress (PND56) |
HPA axis PFC# Behavior# |
Increased stress-induced corticosterone secretion Decreased basal dopamine Increased TH gene methylation Impaired PPI Depression/anxiety-like behaviors |
Niwa et al. (2013) |
| Postmortem brain immunohistochemistry after chronic stress | Rat (SD), M/F |
PND51–58 (M) PND55–62 (F) |
Chronic stress: 7-day restraint stress | Immediately after chronic stress (PND58–62) | mPFC |
M and F(OVX): decreased apical dendrite length F and F(OVX + E): increased apical dendrite length |
Garrett and Wellman (2009) |
| Studies in late adolescents/young adults and adults | |||||||
| Live imaging of DR2/3 binding using PET ([18 F]fallypride) during acute stress | Human, M | 18–30 (mean 22.6) | Acute stress: psychosocial | During acute stress | mPFC | Increased dopamine release during stress | Nagano-Saito et al. (2013) |
| fMRI during acute stress | Human, F | 18–25 (mean 22.6) | Acute stress: psychosocial stress during reward task | During acute stress | mPFC | Decreased reward-related mPFC activation during stress | Ossewaarde et al. (2011) |
| fMRI during acute stress | Human, M | 18–25 | Acute stress during working memory task | During acute stress | DLPFC | Decreased working memory-related DLPFC activation during stress | Qin et al. (2009) |
| Live imaging of DR2/3 binding using PET ([11C]raclopride) | Human, M/F | 18–35 | Acute stress: psychosocial | During acute stress | Striatum | Increased dopamine release during stress | Pruessner et al. (2004) |
| Live imaging of DR2/3 binding using PET ([11C]raclopride) | Human, M/F | 18–29 | Acute stress: psychosocial | During acute stress | Striatum | Increased amphetamine-induced dopamine release during stress | Wand et al. (2007) |
| Live imaging of DR2/3 binding using PET ([11C]raclopride) | Human, M/F | 21–31 | Acute stress: psychosocial | During acute stress | Striatum | Leptin genotype influences dopamine release during stress | Burghardt et al. (2012) |
| Selected studies in adults | |||||||
| In vivo reverse microdialysis during acute stress or PFC corticosterone injection, with/without GR antagonist | Rat (SD), M | PND60–70^ | Acute stress: mild tail pinch | During acute stress | PFC |
Increased dopamine efflux after stress. Attenuated stress-or corticosterone-induced PFC dopamine efflux after administration of GR antagonist RU38486 into the PFC, but not the VTA |
Butts et al. (2011) |
| In vivo microdialysis after acute stress | Rat (Wistar), M/F | PND60–90 | Acute stress: 60 min restraint stress | PND60–90 | Amygdala | Increased amygdala dopamine levels after acute stress in females, but not males | Mitsushima et al. (2006) |
| In vivo microdialysis and adrenalectomy | Rat (SD) | PND90^ | Basal levels and acute mild stress (sham injection) | PND90^ | NAc (shell) | Decreased dopamine release in ADX rats relative to controls and ADX + corticosterone rats | Barrot et al. (2000), Piazza et al. (1996) |
| Postmortem brain analysis after chronic stress | Rat (Wistar) | PND85^ | Chronic stress | PND100^ | Striatum, NAc, VTA | Decreased DR2 density 14 days after stress, but no change in DR2 mRNA. DR2 deficit sustained (>35 days) in stress-sensitive rats, but transient (<35 days) in resilient rats | Zurawek et al. (2013) |
| Wild-type and mutant mice with selective GR inactivation in dopaminergic and dopaminoceptive neurons, plus chronic stress | Mouse, M | PND60–120 | Chronic stress: 10-day social defeat | Immediately after chronic stress |
VTA NAc Behavior PFC, striatum, NAc |
Increased firing of dopamine neurons in WT mice Increased dopamine release in WT mice Social aversion, rescued by treatment with quinpirole (DR2 agonist that suppresses dopamine neuron activity) Abolition of above effects by selective inactivation of GR in dopamine-responsive neurons of the cortex (layers V and VI only), striatum, and NAc |
Barik et al. (2013) |
Abbreviations: PND postnatal day, M male, F female, SD Sprague-Dawley, (m)PFC (medial) prefrontal cortex, DLPFC dorsolateral prefrontal cortex, NAc nucleus accumbens, SN substantia nigra, VTA ventral tegmental area, GR glucocorticoid receptor, DR dopamine receptor, DAT dopamine transporter, MAOA monoamine oxidase A, TH tyrosine hydroxylase, PPI prepulse inhibition, WT wild type, ADX adrenalectomized, OVX ovariectomized, E estrogen, PET positron emission tomography, fMRI functional magnetic resonance imaging, # observations made in DISC1 mutant mice but not WT littermates, ^studies in which animal weights only were published, but study authors were contacted for exact animal ages