Glucocorticoids Regulate Glutamate and GABA Synapse-Specific Retrograde Transmission via Divergent Nongenomic Signaling Pathways

Shi, Dan; Maxson, Marc M.; Franco, Aime T.; Tasker, Jeffrey G.

doi:10.1523/jneurosci.4546-08.2009

Cited by 179 publications

(165 citation statements)

References 47 publications

Supporting

Mentioning

150

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, GR antagonists block this stress-induced increase in hippocampal 2-AG levels (47). Although it is currently unknown how GCs might increase 2-AG levels (i.e., changes in synthesis, release, uptake, or degradation), the effect seems to depend on activation of a G proteincoupled receptor and intracellular cAMP-dependent protein kinase signaling (48).…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory

Atsak

Hauer

Campolongo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

View full text Add to dashboard Cite

There is extensive evidence that glucocorticoid hormones impair the retrieval of memory of emotionally arousing experiences. Although it is known that glucocorticoid effects on memory retrieval impairment depend on rapid interactions with arousalinduced noradrenergic activity, the exact mechanism underlying this presumably nongenomically mediated glucocorticoid action remains to be elucidated. Here, we show that the hippocampal endocannabinoid system, a rapidly activated retrograde messenger system, is involved in mediating glucocorticoid effects on retrieval of contextual fear memory. Systemic administration of corticosterone (0.3-3 mg/kg) to male Sprague-Dawley rats 1 h before retention testing impaired the retrieval of contextual fear memory without impairing the retrieval of auditory fear memory or directly affecting the expression of freezing behavior. Importantly, a blockade of hippocampal CB1 receptors with AM251 prevented the impairing effect of corticosterone on retrieval of contextual fear memory, whereas the same impairing dose of corticosterone increased hippocampal levels of the endocannabinoid 2-arachidonoylglycerol. We also found that antagonism of hippocampal β-adrenoceptor activity with local infusions of propranolol blocked the memory retrieval impairment induced by the CB receptor agonist WIN55,212-2. Thus, these findings strongly suggest that the endocannabinoid system plays an intermediary role in regulating rapid glucocorticoid effects on noradrenergic activity in impairing memory retrieval of emotionally arousing experiences.cannabinoid receptor | norepinephrine | emotional arousal | fear conditioning | posttraumatic stress disorder I t is well-established that glucocorticoid (GC) hormones, released from the adrenal cortex during stressful episodes, can modulate different memory processes (1-4). Although most studies focused on GC effects on the acquisition and consolidation of memory, extensive evidence also indicates that acutely elevated GC levels at the time of retention testing impair the retrieval of memory of spatial and contextual training (5-9). Because a glucocorticoid receptor (GR) agonist infused into the hippocampus before retention induces comparable memory retrieval impairment (10, 11), such findings suggest that GC effects on memory retrieval depend, at least in part, on activation of GRs in the hippocampus. Findings of studies of human subjects are consistent with the findings of animal studies and indicate that exogenous GC administration or exposure to a psychosocial stressor shortly before retention testing impairs retrieval of declarative (mostly episodic) information (7, 12, 13) and reduces hippocampal activity (14). Moreover, previous findings indicate that emotionally arousing information is especially sensitive to the retrieval-impairing effects of GCs (8) and that emotional arousal during the test situation enables GC effects on memory retrieval (15). Findings of recent clinical studies suggest that the administration of stress doses of GCs may have therapeutic v...

show abstract

Section: Discussionmentioning

confidence: 99%

Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory

Atsak

Hauer

Campolongo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

View full text Add to dashboard Cite

show abstract

“…GABA levels oscillate in mood-regulating brain areas like the nucleus accumbens and is also involved in stabilizing circadian rhythms in the SCN, where it acts as an inhibitory neurotransmitter at night and as an excitatory neurotransmitter during the day [37][38][39]. Furthermore, GABA release is facilitated by the GCs [40]. Thus, the circadian clock and the stress response systems overlap extensively, and regulate a multitude of systems that govern affect, reward processing, locomotion and cognition.…”

Section: Connections Between the Clock And Stress Responsementioning

confidence: 99%

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Landgraf

McCarthy

Welsh

2014

Curr Psychiatry Rep

149

100

View full text Add to dashboard Cite

Many psychiatric disorders are characterized by circadian rhythm abnormalities including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to, and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders including posttraumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders.

show abstract

“…Allopregnanolone may prevent stimulation of CRH neurons in the PVN by noradrenaline (Patchev et al, 1994) or it may inhibit CRH neurons by modulating GABA inputs to the PVN by its actions on GABA A receptors. For example, GABA neurons in the peri-PVN area mediate glucocorticoid negative feedback (Di et al, 2009), whereas GABA neurons in the bed nucleus of stria terminalis (Cullinan et al, 2008) can modulate HPA responses to IL-1␤ (Crane et al, 2003).…”

Section: Role Of Allopregnanolonementioning

confidence: 99%

Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone

Brunton¹,

McKay²,

et al. 2009

View full text Add to dashboard Cite

The hypothalamus-pituitary-adrenal (HPA) axis is the major neuroendocrine stress response system. Corticotropin-releasing hormone (CRH) neurons in the parvocellular paraventricular nucleus (pPVN) play a key role in coordinating responses of this system to stressors. The cytokine interleukin-1␤ (IL-1␤), mimicking infection, robustly activates these CRH neurons via a noradrenergic input arising from the nucleus tractus solitarii (NTS). In late pregnancy, HPA axis responses to stressors, including IL-1␤, are attenuated by a central opioid mechanism that auto-inhibits noradrenaline release in the PVN. Here we show that the neuroactive progesterone metabolite allopregnanolone induces these changes in HPA responsiveness to IL-1␤ in pregnancy. In late pregnancy, inhibition of 5␣-reductase (an allopregnanolone-synthesizing enzyme) with finasteride restored HPA axis responses (rapidly increased pPVN CRH mRNA expression, ACTH, and corticosterone secretion) to IL-1␤. Conversely, allopregnanolone reduced HPA responses in virgin rats. In late pregnancy, activity of the allopregnanolone-synthesizing enzymes (5␣-reductase and 3␣-hydroxysteroid dehydrogenase) was increased in the hypothalamus as was mRNA expression in the NTS and PVN. Naloxone, an opioid antagonist, restores HPA axis responses to IL-1␤ in pregnancy but had no additional effect after finasteride, indicating a causal connection between allopregnanolone and the endogenous opioid mechanism. Indeed, allopregnanolone induced opioid inhibition over HPA responses to IL-1␤ in virgin rats. Furthermore, in virgin rats, allopregnanolone treatment increased, whereas in pregnant rats finasteride decreased proenkephalin-A mRNA expression in the NTS. Thus, in pregnancy, allopregnanolone induces opioid inhibition over HPA axis responses to immune challenge. This novel opioid-mediated mechanism of allopregnanolone action may alter regulation of other brain systems in pregnancy.

show abstract

Glucocorticoids Regulate Glutamate and GABA Synapse-Specific Retrograde Transmission via Divergent Nongenomic Signaling Pathways

Cited by 179 publications

References 47 publications

Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory

Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Central Opioid Inhibition of Neuroendocrine Stress Responses in Pregnancy in the Rat Is Induced by the Neurosteroid Allopregnanolone

Contact Info

Product

Resources

About