The dorsal raphe nucleus exerts opposed control on generalized anxiety and panic-related defensive responses in rats

Sena, Lı́gia Moreiras; Bueno, Cíntia Heloína; Pobbe, Roger L.H.; Andrade, Telma Gonçalves Carneiro Spera de; Zangrossi, Hélio; Viana, Milena de Barros

doi:10.1016/s0166-4328(02)00399-6

Cited by 87 publications

(57 citation statements)

References 26 publications

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“…If this is so, then the present results indicate that control is important in regulating generalized anxiety. It has been argued that the activation of DRN 5-HT neurons is uniquely related to generalized anxiety [13,41], and so the dissociation between the effects of control on social exploration and the lack of effect on the elevated plus maze is consistent with a critical role of DRN 5-HT in mediating the effects of control on anxiety.…”

Section: Discussionmentioning

confidence: 98%

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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Section: Discussionmentioning

confidence: 98%

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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“…Five days after surgery, the animals were exposed to one of the open arms of the ETM for 30 min as described by Sena et al (18). It has been shown that pre-exposure renders the escape task more sensitive to the effects of antipanic drugs because it shortens the latencies of withdrawal from the open arm during the test (18).…”

Section: Methodsmentioning

confidence: 99%

“…It has been shown that pre-exposure renders the escape task more sensitive to the effects of antipanic drugs because it shortens the latencies of withdrawal from the open arm during the test (18). On the next day, rats were injected (0.2 µL, 2 min) with muscimol (0.5 and 1.0 nmol) or saline.…”

Section: Methodsmentioning

confidence: 99%

Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and anxiety-related responses in rats

Nascimento

Zangrossi

Viana

2010

Braz J Med Biol Res

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“…active vs. passive coping (Cryan et al, 2005)). Sena et al (2003) have suggested that that the DRN exerts opposing effects on one-way escape and inhibitory avoidance, suppressing one response when the other is activated (Sena et al, 2003). Johnson et al (2004) have proposed that control of behavioral response to anxiogenic stimuli may be subregionally specific, with the dorsolateral DRN involved in passive coping; with the ventromedial DRN involved in active escape responses .…”

Section: Serotonergic Gene Expression Following Chronic Crf Receptor mentioning

confidence: 99%

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

et al. 2007

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Corticotropin releasing factor (CRF) family peptides play key roles in integrating neural responses to stress. Both major CRF receptors have been pharmacologically identified in the dorsal raphe nucleus (DRN), a stress sensitive and internally heterogeneous nucleus supplying many forebrain regions with serotonergic input. Despite the involvement of chronic stress and serotonergic dysfunction in human mood and anxiety disorders, little is known about the effects of chronic CRF receptor activation on the DRN. We infused ovine CRF (1ng/hr), urocortin II (UCNII, 1ng/hr), or vehicle alone into rat DRN over 6 days. During infusion, animals were allowed to freely explore an open field for 15 minutes on each of two days, with the addition of a novel object on the second day. Following behavioral testing, 5-HT 1A , 5-HT 1B , serotonin transporter (SERT), and tryptophan hydroxylase-2 (Tph2) expression were examined through the DRN by in situ hybridization. Ovine CRF infusion resulted in significantly decreased novel object touches, climbs, as well as increased latency to first novel object contact. UCNII had a similar but less dramatic effect, decreasing only climbing behavior. Both ovine CRF and UCNII blunted the decrease in corner time expected on reexposure to the open field. Both peptides also produced regionally specific changes in gene expression: 5-HT 1A expression was increased 30% in the mid-rostral ventromedial DRN, while SERT was decreased by 30% in the mid-caudal shell dorsomedial DRN. There also appeared to be a shift in the relative level of Tph2 expression between the ventromedial and core dorsomedial DRN at the mid-rostral level. Changes in 5-HT 1A , SERT, and relative Tph2 mRNA abundance were correlated with novel object exploration. These findings suggest chronic intra-DRN administration of CRF agonists decreases exploratory behavior, while producing subregionally limited changes in serotonergic gene expression. These studies may be relevant to mechanisms underlying behavioral changes after chronic stress. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDepression and anxiety disorders are among the leading causes of morbidity, mortality, and disability in the United States (Greenberg et al., 2003). They are often comorbid, and both are highly associated with chronic exposure to stress. Multiple lines of evidence suggest that chronic and inescapable stress produce long lasting effects on brain function and behavior that play a prominent role in the development, maintenance, and recurrence of both depression and a variety of anxiety disorders (Gulley and Nemeroff, 1993, Arborelius et al., 1999, Ressler and Nemeroff, 2000.Altered serotonin neurotransmission appears to be a central mechanism inducing both depressive (Maes and Meltzer, 1995) and anxiety disorders (Ressler and Nemeroff, 2000). The majority of serotonergic fibers to forebrain regions thought to be involved in mood and anxiety regulation arise from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) ...

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The dorsal raphe nucleus exerts opposed control on generalized anxiety and panic-related defensive responses in rats

Cited by 87 publications

References 26 publications

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

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

Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and anxiety-related responses in rats

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

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