Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor

Grahn, Ruth E.; Will, Melissa L.; Hammack, Sayamwong E.; Maswood, Sharmin; McQueen, Matthew B.; Watkins, Linda R.; Maier, Steven F.

doi:10.1016/s0006-8993(99)01208-1

Cited by 267 publications

(239 citation statements)

References 85 publications

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“…We found previously that IS produces greater activation of DRN 5-HT neurons than equated ES as assessed by c-Fos protein expression in 5-HT-labeled neurons (Grahn et al, 1999). This effect of controllability was especially prominent in middle and caudal regions of the DRN.…”

Section: C-fos Expression In 5-ht-labeled Neurons In the Drnmentioning

confidence: 67%

“…Fos expression did not differ in the MUS and VEH HC day 1 groups, and so these groups were pooled. It should be noted that previous work (Grahn et al, 1999;Takase et al, 2004;Amat et al, 2005) has indicated that there is virtually no Fos expression in 5-HT-labeled DRN neurons in home-cage control subjects. Thus, it can be presumed that the Fos observed was induced by the IS.…”

Section: C-fos Expression In 5-ht-labeled Neurons In the Drnmentioning

confidence: 87%

“…These and related behavioral changes, which have been called "learned helplessness" (Maier and Seligman, 1976), have been linked to IS-induced changes in brainstem nuclei, most notably the serotonergic (5-HT) dorsal raphe nucleus (DRN) and the noradrenergic locus ceruleus (Weiss and Simson, 1986). With regard to the DRN, IS produces greater activation than does equated ES (Amat et al, 1998;Maswood et al, 1998;Grahn et al, 1999), and this activation is critical to the production of the behavioral effects of IS (Maier et al, 1995). However, the DRN is a brainstem nucleus unlikely to detect whether a stressor is controllable, and thus DRN activation during stress is likely regulated by a "higher" structure.…”

Section: Introductionmentioning

confidence: 99%

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Previous Experience with Behavioral Control over Stress Blocks the Behavioral and Dorsal Raphe Nucleus Activating Effects of Later Uncontrollable Stress: Role of the Ventral Medial Prefrontal Cortex

Amat

Paul²,

Zarza³

et al. 2006

J. Neurosci.

207

212

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Previous experience with stressors over which the subject has behavioral control blocks the typical behavioral consequences of subsequent exposure to stressors over which the organism has no behavioral control. The present experiments explored the involvement of the ventral medial prefrontal cortex (mPFCv) in mediating this "immunizing" or resilience producing effect of an initial experience with control. Behavioral immunization was blocked by inactivation of the mPFCv with muscimol at the time of the initial experience with control, as well as at the time of the later exposure to uncontrollable stress. Inhibition of protein synthesis within the mPFCv by anisomycin also blocked immunization when administered at the time of the initial controllable stress but had no effect when administered at the time of the later uncontrollable stress. Additional experiments found that the initial experience with control blocks the intense activation of serotonergic cells in the dorsal raphe nucleus that would normally be produced by uncontrollable stress, providing a mechanism for behavioral immunization. Furthermore, mPFCv activity during the initial controllable stressor was required for this effect to occur. These results suggest that the mPFCv is needed both to process information about the controllability of stressors and to utilize such information to regulate responses to subsequent stressors. Moreover, the mPFCv may be a site of storage or plasticity concerning controllability information. These results are consistent with recent research in other domains that explore the functions of the mPFCv.

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Section: C-fos Expression In 5-ht-labeled Neurons In the Drnmentioning

confidence: 67%

Section: C-fos Expression In 5-ht-labeled Neurons In the Drnmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Previous Experience with Behavioral Control over Stress Blocks the Behavioral and Dorsal Raphe Nucleus Activating Effects of Later Uncontrollable Stress: Role of the Ventral Medial Prefrontal Cortex

Amat

Paul²,

Zarza³

et al. 2006

J. Neurosci.

207

212

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show abstract

“…Furthermore, evidence shows that prior exposure to acute or chronic stressors can result in behavioral and pharmacological sensitization effects caused by changes dopaminergic (Pani et al, 2000;de Jong et al, 2005) and serotonergic tone (Adell et al, 1988;Chung et al, 2000;Matuszewich and Yamamoto, 2003). In support of this view, Watkins and Maier have shown that the habenula is essential for the normal sensitization of DRN neurons after uncontrollable stress (Maier et al, 1995;Maswood et al, 1998;Grahn et al, 1999;Amat et al, 2001). The stress-induced alteration in the habenulo-DRN pathway results in increase excitation of DRN 5-HT neurons and changes in subsequent stress behaviors.…”

Section: Discussionmentioning

confidence: 95%

Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion

Heldt

Ressler

2006

Brain Research

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The habenula complex modulates the a ctivity of dopamine and serotonin systems in the brain. An important question remains whether there is a link between habenula dysfunction and monoaminerelated disorders, such as schizophrenia. In this study, we describe an interaction between habenula lesions and stress that produces long-lasting effects on behavior. Mice received control lesions or bilateral electrolytic lesions of the habenula and were tested for fear-potentiated startle and freezing measures of conditioned fear. They w ere also tested for prepulse inhibition (PPI) and locomotor activity in the presence or absence of a dopaminergic agonist (apomorphine) or an atypical antipsychotic with mixed dopamine/serotonin antagonist properties (clozapine). There were no detectable effects of habenula lesions on fear conditioning and no effects on PPI in the absence o f stress. However, following conditioned fear stress, habenula-lesioned animals showed decreased PPI which normalized with clozapine. Lesioned animals also showed diminished activity at baseline, with hyperlocomotion following apomorphine. These data support the hypothesis that the habenula may be normally involved in stress-dependent regulation of monoamine systems.

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“…Sensitization of DRN 5-HT neurons occurs because IS, relative to ES, selectively activates DRN 5-HT neurons (Grahn et al, 1999). This intense activation produces large amounts of extracellular 5-HT in projection regions of the DRN such as the basolateral amygdala (Amat et al, 1998a, b) as well as in the DRN itself (Amat et al, 2001;Maswood et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

Bland

Hargrave

Pepin

et al. 2003

Neuropsychopharmacol

133

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It has previously been shown that inescapable (IS) but not escapable (ES) stress potentiates the rewarding properties of morphine as measured by conditioned place preference and psychomotor activation, and that this potentiation may be mediated by dorsal raphe nucleus (DRN) serotonin (5-HT) neurons. The medial prefrontal cortex (mPFC) has been implicated in both reward and stress, and is a projection region of the DRN. The mPFC also contains dopaminergic afferents from the ventral tegmental area, which has been the focus of many studies exploring both the rewarding properties of drugs and the aversive properties of stress. The role of the mPFC in stress/ drug reactivity interactions is largely unknown. The present study usedin vivo microdialysis to examine 5-HT and dopamine (DA) efflux in the mPFC of rats during IS, ES or no stress (NS). IS and ES rats received the stressor in yoked pairs. The stressor consisted of tailshocks that could be terminated for both rats by the ES rats. Large increases in 5-HT and DA levels were observed during IS but not ES or NS. DA and 5-HT efflux were also measured 24 h later in the same rats in response to morphine (3 mg/kg) or saline. Sustained increases in 5-HT levels were observed after morphine in rats that had previously received IS but not in rats that had received ES or NS. No changes in DA efflux were observed after morphine. Thus, 5-HT and DA in the mPFC may be involved in stressor controllability effects, and the sensitization of 5-HT neurons by IS extends to the mPFC and to morphine as a challenge.

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Activation of serotonin-immunoreactive cells in the dorsal raphe nucleus in rats exposed to an uncontrollable stressor

Cited by 267 publications

References 85 publications

Previous Experience with Behavioral Control over Stress Blocks the Behavioral and Dorsal Raphe Nucleus Activating Effects of Later Uncontrollable Stress: Role of the Ventral Medial Prefrontal Cortex

Previous Experience with Behavioral Control over Stress Blocks the Behavioral and Dorsal Raphe Nucleus Activating Effects of Later Uncontrollable Stress: Role of the Ventral Medial Prefrontal Cortex

Lesions of the habenula produce stress- and dopamine-dependent alterations in prepulse inhibition and locomotion

Stressor Controllability Modulates Stress-Induced Dopamine and Serotonin Efflux and Morphine-Induced Serotonin Efflux in the Medial Prefrontal Cortex

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