8-OH-DPAT microinjected in the region of the dorsal raphe nucleus blocks and reverses the enhancement of fear conditioning and interference with escape produced by exposure to inescapable shock.

Maier, Steven F.; Grahn, Ruth E.; Watkins, Linda R.

doi:10.1037/0735-7044.109.3.404

Cited by 146 publications

(136 citation statements)

References 46 publications

(89 reference statements)

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“…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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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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“…[1,24]). IS in one environment later increases freezing immediately after footshock in a different environment and interferes with shuttlebox escape, but ES has no effect [22].…”

Section: Introductionmentioning

confidence: 99%

“…The extent to which ES could block or reduce later IS effects on social exploration and sucrose preference is unknown. With regard to neural mediation ,IS-induced changes in post-shock freezing and shuttle escape depend upon dorsal raphé nucleus (DRN) activation at the time of IS [24], this activation being prevented by behavioral control [1] (for review see [26]). The role of the DRN has only been examined with escape and freezing to shock as measures.…”

Section: Introductionmentioning

confidence: 99%

The role of prior stressor controllability and the dorsal raphé nucleus in sucrose preference and social exploration

Christianson

Paul

Irani

et al. 2008

Behavioural Brain Research

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Research investigating how control over stressors affects behavior often utilizes freezing and shuttle escape learning as the behavioral endpoints. These endpoints have been argued to reflect anxious or depressed states, but these descriptions are problematic. The present study sought to determine the impact of stressor controllability and the dorsal raphé nucleus (DRN) on sucrose preference and juvenile social exploration, putative measures of anhedonia and anxiety that are commonly used in studies of stress per se. In Experiment 1 rats were exposed to escapable (ES) or yoked-inescapable (IS) tailshocks. In Experiment 2 ES or IS was given 7 days before all rats received IS. In Experiment 3 the DRN was inactivated during IS by microinjection of 8-OH-DPAT. Sucrose preference and social exploration were tested for several days after stress. A fourth experiment confirmed that juvenile social exploration is sensitive to traditional β-carboline and benzodiazepine manipulations. Both ES and IS reduced sucrose preference, but only IS reduced social exploration. Prior treatment with ES prevented the effect of IS on social exploration but did not prevent the effect of IS on sucrose preference and inactivation of the DRN prevented the effect of IS on social exploration but did not change sucrose preference. The present results indicate that social exploration but not sucrose preference is sensitive to prior stressor controllability, and that DRN activation mediates the effect of IS on social exploration. We argue that DRN-5-HT activation mediates a state of generalized anxiety produced by uncontrollable stress and that juvenile social exploration is a useful behavioral endpoint in stressor controllability studies.

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“…For example, exposure to inescapable shock (IS) but not equal amounts and durations of escapable shock (ES) leads to later failure to learn to escape shocks in a different situation (Maier and Seligman, 1976). Other behavioral outcomes resulting from exposure to IS but not ES include an exaggeration of fear conditioning to a context (Maier et al, 1995), increases in neophobia (Minor et al, 1994), and reductions in social interaction (Short and Maier, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…Activation and sensitization of serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN) is necessary for producing the behavioral effects of uncontrollable stress (Maier et al, 1995). Sensitization of DRN 5-HT neurons occurs because IS, relative to ES, selectively activates DRN 5-HT neurons (Grahn et al, 1999).…”

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

134

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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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8-OH-DPAT microinjected in the region of the dorsal raphe nucleus blocks and reverses the enhancement of fear conditioning and interference with escape produced by exposure to inescapable shock.

Cited by 146 publications

References 46 publications

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

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

The role of prior stressor controllability and the dorsal raphé nucleus in sucrose preference and social exploration

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

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