scholarly journals Allopregnanolone mediates affective switching through modulation of oscillatory states in the basolateral amygdala

2021 ◽  
Author(s):  
Pantelis Antonoudiou ◽  
Phillip LW Colmers ◽  
Najah L Walton ◽  
Grant L Weiss ◽  
Anne C Smith ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Post Partum ◽  
Critical Role ◽  
Behavioral Outcomes ◽  
Theta Oscillations ◽  
Allosteric Modulators ◽  
Post Partum Depression ◽  
Antidepressant Effects ◽  
Behavioral States ◽  
Network States

AbstractBrexanolone (allopregnanolone), was recently approved by the FDA for the treatment of post-partum depression, demonstrating long-lasting antidepressant effects. Despite our understanding of the mechanism of action of neurosteroids as positive allosteric modulators (PAMs) of GABAa receptors, we still do not fully understand how allopregnanolone exerts these persistent antidepressant effects. Here, we demonstrate that allopregnanolone and similar synthetic neuroactive steroid analogs, SGE-516 (tool-compound) and zuranolone (SAGE-217, investigational-compound), are capable of modulating oscillatory states across species, which we propose may contribute to long-lasting changes in behavioral states. We identified a critical role for interneurons in generating oscillations in the basolateral amygdala (BLA) and a role for delta-containing GABAaRs in mediating the ability of neurosteroids to modulate network and behavioral states. Actions of allopregnanolone in the BLA is sufficient to alter behavioral states and enhance BLA high-theta oscillations (6-12Hz) through delta-containing GABAa receptors, a mechanism distinct from other GABAa PAMs, such as benzodiazepines. Moreover, treatment with the allopregnanolone analog SGE-516 induces long-lasting protection from chronic stress-induced disruption of network states, which correlates with improved behavioral outcomes. Our findings demonstrate a novel molecular and cellular mechanism mediating the well-established anxiolytic and antidepressant effects of neuroactive steroids.

scholarly journals Neuromodulation-induced burst firing in parvalbumin interneurons of the basolateral amygdala mediates transition between fear-associated network and behavioral states

2021 ◽  
Author(s):  
Xin Fu ◽  
Eric Teboul ◽  
Jamie Maguire ◽  
Jeffrey G Tasker
Keyword(s):  
Basolateral Amygdala ◽  
Critical Role ◽  
Field Potential ◽  
Gamma Oscillations ◽  
Receptor Activation ◽  
Neuron Activity ◽  
Behavioral States ◽  
Fear Expression

Network orchestration of behavioral states involves coordinated oscillations within and between brain regions. The network communication between the basolateral amygdala (BLA) and the medial prefrontal cortex (PFC) plays a critical role in fear expression. Neuromodulatory systems play an essential role in regulating changes between behavioral states, however, a mechanistic understanding of how amygdalar circuits mediate transitions between brain and behavioral states remains largely unknown. Here, we examine the role of Gq-mediated neuromodulation of parvalbumin (PV)-expressing interneurons in the BLA in coordinating network and behavioral states using combined chemogenetics, patch clamp and field potential recordings. We demonstrate that Gq-signaling via hM3D designer receptor and α1 adrenoreceptor activation shifts the pattern of activity of the PV interneurons from tonic to phasic by stimulating a previously unknown, highly stereotyped bursting pattern of activity. This, in turn, generates bursts of inhibitory postsynaptic currents (IPSCs) and phasic firing in BLA principal neurons. The Gq-induced transition from tonic to phasic firing in BLA PV interneurons suppressed amygdalo-frontal gamma oscillations in vivo, consistent with the critical role of tonic PV neuron activity in gamma generation. The suppression of gamma oscillations by hM3D and α1 receptor activation in BLA PV interneurons also facilitated fear memory recall, in line with the inhibitory effect of gamma on fear expression. Thus, our data reveal a BLA parvalbumin neuron-specific neuromodulatory mechanism that mediates the transition to a fear-associated brain network state via regulation of amygdalo-frontal gamma oscillations.

scholarly journals Post-partum Depression-It’s Time to Pay Maximum Attention

2018 ◽  
Vol 04 (01) ◽  
Author(s):  
Ibrahim Abdul Rahman ◽  
Uzair Yaqoob ◽  
Tariq Ali Bhatti
Keyword(s):  
Post Partum ◽  
Post Partum Depression

scholarly journals Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression

2003 ◽  
Vol 182 (5) ◽  
pp. 412-419 ◽  
Author(s):  
Peter J. Cooper ◽  
Lynne Murray ◽  
Anji Wilson ◽  
Helena Romaniuk
Keyword(s):  
Primary Care ◽  
Postnatal Depression ◽  
Post Partum ◽  
Psychodynamic Therapy ◽  
Term Effect ◽  
Short Term ◽  
Post Partum Depression ◽  
Maternal Mood ◽  
Long Term Effect

BackgroundPsychological interventions for postnatal depression can be beneficial in the short term but their longer-term impact is unknown.AimsTo evaluate the long-term effect on maternal mood of three psychological treatments in relation to routine primary care.MethodWomen with post-partum depression (n=193) were assigned randomly to one of four conditions: routine primary care, non-directive counselling, cognitive–behavioural therapy or psychodynamic therapy. They were assessed immediately after the treatment phase (at 4.5 months) and at 9, 18 and 60 months post-partum.ResultsCompared with the control, all three treatments had a significant impact at 4.5 months on maternal mood (Edinburgh Postnatal Depression Scale, EPDS). Only psychodynamic therapy produced a rate of reduction in depression (Structured Clinical Interview for DSM–III–R) significantly superior to that of the control. The benefit of treatment was no longer apparent by 9 months post-partum. Treatment did not reduce subsequent episodes of post-partum depression.ConclusionsPsychological intervention for post-partum depression improves maternal mood (EPDS) in the short term. However, this benefit is not superior to spontaneous remission in the long term.

Post-partum depression – prevention, diagnosis and therapeutic approach

Medic ro ◽  
2021 ◽  
Vol 1 (139) ◽  
pp. 50
Author(s):  
Roxana Anamaria Viţelariu ◽  
Diana Vulea ◽  
Remus Şipoş
Keyword(s):  
Therapeutic Approach ◽  
Post Partum ◽  
Depression Prevention ◽  
Post Partum Depression

scholarly journals Discordant Effects of Cannabinoid 2 Receptor Antagonism/Inverse Agonism During Adolescence on Pavlovian and Instrumental Reward Learning in Adult Male Rats

2021 ◽  
Vol 13 ◽  
Author(s):  
Danna Ellner ◽  
Bryana Hallam ◽  
Jude A. Frie ◽  
Hayley H. A. Thorpe ◽  
Muhammad Shoaib ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Critical Role ◽  
Behavioral Outcomes ◽  
Endocannabinoid System ◽  
Developmental Trajectory ◽  
Male Rats ◽  
Reward Learning ◽  
Adolescent Male ◽  
High Dose ◽  
Lever Pressing

The endocannabinoid system is responsible for regulating a spectrum of physiological activities and plays a critical role in the developing brain. During adolescence, the endocannabinoid system is particularly sensitive to external insults that may change the brain’s developmental trajectory. Cannabinoid receptor type 2 (CB2R) was initially thought to predominantly function in the peripheral nervous system, but more recent studies have implicated its role in the mesolimbic pathway, a network largely attributed to reward circuitry and reward motivated behavior, which undergoes extensive changes during adolescence. It is therefore important to understand how CB2R modulation during adolescence can impact reward-related behaviors in adulthood. In this study, adolescent male rats (postnatal days 28–41) were exposed to a low or high dose of the CB2R antagonist/inverse agonist SR144528 and Pavlovian autoshaping and instrumental conditional behavioral outcomes were measured in adulthood. SR144528-treated rats had significantly slower acquisition of the autoshaping task, seen by less lever pressing behavior over time [F(2, 19) = 5.964, p = 0.010]. Conversely, there was no effect of adolescent SR144528 exposure on instrumental conditioning. These results suggest that modulation of the CB2R in adolescence differentially impacts reward-learning behaviors in adulthood.

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