scholarly journals Ketamine Administration Reverses Corticosterone-Induced Alterations in Excitatory and Inhibitory Transmission in the Rat Dorsal Raphe Nucleus

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Joanna Sowa ◽  
Magdalena Kusek ◽  
Bartosz Bobula ◽  
Grzegorz Hess ◽  
Krzysztof Tokarski
Keyword(s):  
Chronic Stress ◽  
Dorsal Raphe Nucleus ◽  
Ex Vivo ◽  
Nmda Receptor Antagonist ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Inhibitory Transmission ◽  
Postsynaptic Currents ◽  
Corticosterone Treatment ◽  
Dorsal Raphé

Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects in human patients and ameliorates depressive-like behavioral effects of chronic stress in animal models. Chronic stress and elevated corticosterone levels have been shown to modify serotonin (5-HT) neurotransmission, and ketamine’s antidepressant-like activity involves a 5-HT-dependent mechanism. However, it is not known if and how ketamine affects the electrophysiological characteristics of neurons and synaptic transmission within the dorsal raphe nucleus (DRN), the main source of 5-HT forebrain projections. Our study was aimed at investigating the effects of a single ketamine administration on excitatory and inhibitory transmission in the DRN of rats which had previously been administered corticosterone twice daily for 7 days. Spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were then recorded from DRN projection cells in ex vivo slice preparations obtained 24 h after ketamine injection. Repeated corticosterone administration increased sEPSC frequency and decreased sIPSC frequency in DRN projection cells. There were no changes either in the amplitude of postsynaptic currents or in the excitability of these cells. In slices prepared from rats with ketamine administered after the end of corticosterone treatment, the frequencies of sEPSCs and sIPSCs were similar to those in control preparations. These data indicate that a single administration of ketamine reversed the effects of corticosterone on excitatory and inhibitory transmission in the DRN.

scholarly journals Serotonergic plasticity in the dorsal raphe nucleus characterizes susceptibility and resilience to anhedonia

2019 ◽  
Author(s):  
Nandkishore Prakash ◽  
Christiana J. Stark ◽  
Maria N. Keisler ◽  
Lily Luo ◽  
Andre Der-Avakian ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Dorsal Raphe Nucleus ◽  
Dorsal Raphe ◽  
Raphe Nucleus ◽  
Serotonergic System ◽  
Male Rats ◽  
Vulnerability To Stress ◽  
Neurotransmitter Plasticity ◽  
New Treatments ◽  
Dorsal Raphé

ABSTRACTChronic stress induces anhedonia in susceptible, but not resilient individuals, a phenomenon observed in humans as well as animal models, but the molecular mechanisms underlying susceptibility and resilience are not well understood. We hypothesized that the serotonergic system, which is implicated in stress, reward and antidepressant therapy, may play a role. We found that plasticity of the serotonergic system contributes to the differential vulnerability to stress displayed by susceptible and resilient animals. Stress-induced anhedonia was assessed in adult male rats using social defeat and intracranial self-stimulation (ICSS), while changes in serotonergic phenotype were investigated using immunohistochemistry and in situ hybridization. Susceptible, but not resilient, rats displayed an increased number of neurons expressing the biosynthetic enzyme for serotonin, tryptophan-hydroxylase-2 (TPH2), in the ventral subnucleus of the dorsal raphe nucleus (DRv). Further, a decrease in the number of DRv glutamatergic neurons was observed in all stressed animals. This neurotransmitter plasticity is dependent on DR activity, as was revealed by chemogenetic manipulation of the central amygdala, a stress-sensitive nucleus that forms a major input to the DR. Activation of amygdalar corticotropin releasing hormone (CRH)+ neurons abolished the increase in DRv TPH2+ neurons and ameliorated stress-induced anhedonia in susceptible animals. These findings show that activation of amygdalar projections induces resilience, and suppresses the gain of serotonergic phenotype in the DR that is characteristic of susceptible animals. This molecular signature of vulnerability to stress-induced anhedonia and the active nature of resilience could be a target of new treatments for stress-related disorders like depression.SIGNIFICANCE STATEMENTDepression and other mental disorders can be induced by chronic or traumatic stressors. However, some individuals are resilient and do not develop depression in response to chronic stress. A complete picture of the molecular differences between susceptible and resilient individuals is necessary to understand how plasticity of limbic circuits is associated with the pathophysiology of stress-related disorders. Using a rodent model, our study identifies a novel molecular marker of susceptibility to stress-induced anhedonia, a core symptom of depression, and a means to modulate it. These findings will guide further investigation into cellular and circuit mechanisms of resilience, and the development of new treatments for depression.

The role of serotonin in depression and anxiety

1998 ◽  
Vol 13 (S2) ◽  
pp. 57s-63s ◽  
Author(s):  
JFW Deakin
Keyword(s):  
Chronic Stress ◽  
Dorsal Raphe Nucleus ◽  
Experimental Tests ◽  
Dorsal Raphe ◽  
Good Evidence ◽  
Raphe Nucleus ◽  
Panic Attacks ◽  
Behavioural Inhibition ◽  
Anticipatory Anxiety ◽  
Dorsal Raphé

SummaryThe different coping responses to three types of aversive events - future threats, acute events and chronic stress — may be modulated by 5HT projections. Dysfunction in these coping mechanisms could cause, respectively: generalised anxiety disorder, panic, and depression. This theory proposes that dorsal raphe nucleus projections to 5HT2 and 5HT1D receptors mediate anticipatory anxiety and normally motivate avoidance of threats. The brain aversion system may be held in check by dorsal raphe nucleus 5HT projections to mediate behavioural inhibition during anticipatory anxiety. Proximal aversive stimuli such as pain and asphyxia elicit the fight-flight reflex mediated by the amygdala-hypothalamic-periaqueductal grey brain aversion system. Panic attacks may thus be due to spontaneous activation of this system. Median raphe projections to 5HT1A receptors have been implicated in adaptation to chronic stress-resilence. There is good evidence that 5HT1A function breaks down in depression and causes the depressed state. Experimental tests of this theory suggest that viewing anxiety, panic, and depression as dysfunctions in neurochemically and anatomically specific coping systems is heuristically useful.

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