The median raphe nucleus in anxiety revisited

Andrade, Telma Gonçalves Carneiro Spera de; Zangrossi, Hélio; Graeff, Frederico Guilherme

doi:10.1177/0269881113499208

Cited by 53 publications

(43 citation statements)

References 97 publications

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“…These anatomic analyses support theoretical assumptions that the MRN-dorsal hippocampus pathway is a critical component in stress resistance (Deakin and Graeff, 1991) and in anxiogenesis (Andrade et al., 2013) by integrating Gray's “behavioral inhibition system” (Gray and McNaughton, 2000). …”

Section: Introductionsupporting

confidence: 77%

Interaction between estradiol and 5-HT1A receptors in the median raphe nucleus on acquisition of aversive information and association to the context in ovariectomized rats

Andrade

Silva

Batistela

et al. 2017

Neurobiology of Stress

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The median raphe nucleus (MRN) is related to stress resistance and defensive responses, a crucial source of serotonergic neurons that project to prosencephalic structures related to stress and anxiety. Estrogen receptors were identified in this mesencephalic structure. It is possible that the estrogen action is related to serotonin effect on somatodendritic 5-HT1A receptors, inhibiting the function of serotonergic neurons and thus preventing of the stress effect and inducing anxiolysis. So, in order to evaluate these aspects, female Wistar rats were ovariectomized and 21 days later were given a direct microinjection of estradiol benzoate (EB) (1200 ng) into the MRN, preceded by microinjections of saline or WAY100.635 (100 ng), a 5-HT1A receptor antagonist. Immediately after the two microinjections, the ovariectomized rats were conditioned with an aversive event (foot shock) session in a Skinner box. Twenty-four hours later, they were exposed to the same context in a test session for 5 min for behavioral assessment: freezing, rearing, locomotion, grooming, and autonomic responses (fecal boluses and micturition). EB microinjection in the MRN prior to the exposure of animals to the foot shocks in the conditioning session did not alter their behavior in this session, but neutralized the association of the aversive experience to the context: there was a decrease in the expression of freezing and an increased rearing activity in the test session. This effect was reversed by prior microinjection of WAY100.635. In conclusion, EB acted on serotonergic neurons in the MRN of the ovariectomized rats, impairing the association of the aversive experience to the context, by co-modulating the functionality of somatodendritic 5-HT1A.

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Section: Introductionsupporting

confidence: 77%

Interaction between estradiol and 5-HT1A receptors in the median raphe nucleus on acquisition of aversive information and association to the context in ovariectomized rats

Andrade

Silva

Batistela

et al. 2017

Neurobiology of Stress

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“…In this regard, Gray et al[81] have argued that the amygdala may underpin the neurovegetative arousal and affective components of anxiety, whereas the dorsal hippocampus may regulate cognitive manifestations, such as worry. This suggestion is supported by the reported interaction between the dorsal hippocampus and the prefrontal cortex underpinning fear learning and memory[80,82]. According to a recent study by Ohmura et al[83] the ventral (anterior part in humans) hippocampus may be involved in inappropriate retrieval of fear memory in PD.…”

Section: Resultsmentioning

confidence: 90%

“…Generally, evidence derived from animal studies points to a relevant role of this raphe nucleus in the regulation of anxiety, but not of panic. This can be achieved through the serotonergic pathway that rises from the MRN to the dorsal hippocampus[80]. Alternatively, the DRN seems to participate in both anxiety and panic.…”

Section: Resultsmentioning

confidence: 99%

Functional neuroanatomy in panic disorder: Status quo of the research

Sobanski¹,

Wagner²

2017

WJP

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AIMTo provide an overview of the current research in the functional neuroanatomy of panic disorder.METHODSPanic disorder (PD) is a frequent psychiatric disease. Gorman et al (1989; 2000) proposed a comprehensive neuroanatomical model of PD, which suggested that fear- and anxiety-related responses are mediated by a so-called “fear network” which is centered in the amygdala and includes the hippocampus, thalamus, hypothalamus, periaqueductal gray region, locus coeruleus and other brainstem sites. We performed a systematic search by the electronic database PubMed. Thereby, the main focus was laid on recent neurofunctional, neurostructural, and neurochemical studies (from the period between January 2012 and April 2016). Within this frame, special attention was given to the emerging field of imaging genetics.RESULTSWe noted that many neuroimaging studies have reinforced the role of the “fear network” regions in the pathophysiology of panic disorder. However, recent functional studies suggest abnormal activation mainly in an extended fear network comprising brainstem, anterior and midcingulate cortex (ACC and MCC), insula, and lateral as well as medial parts of the prefrontal cortex. Interestingly, differences in the amygdala activation were not as consistently reported as one would predict from the hypothesis of Gorman et al (2000). Indeed, amygdala hyperactivation seems to strongly depend on stimuli and experimental paradigms, sample heterogeneity and size, as well as on limitations of neuroimaging techniques. Advanced neurochemical studies have substantiated the major role of serotonergic, noradrenergic and glutamatergic neurotransmission in the pathophysiology of PD. However, alterations of GABAergic function in PD are still a matter of debate and also their specificity remains questionable. A promising new research approach is “imaging genetics”. Imaging genetic studies are designed to evaluate the impact of genetic variations (polymorphisms) on cerebral function in regions critical for PD. Most recently, imaging genetic studies have not only confirmed the importance of serotonergic and noradrenergic transmission in the etiology of PD but also indicated the significance of neuropeptide S receptor, CRH receptor, human TransMEMbrane protein (TMEM123D), and amiloride-sensitive cation channel 2 (ACCN2) genes.CONCLUSIONIn light of these findings it is conceivable that in the near future this research will lead to the development of clinically useful tools like predictive biomarkers or novel treatment options.

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“…Although the dorsal raphe nucleus and its projections (e.g., to the amygdala or the medial prefrontal cortex) have been well implicated in depression and anxiety, the role of the median raphe nucleus (MRN) and its projections (e.g., to the dorsal hippocampus [DH]) have been only recently investigated (Andrade et al, 2013;Deakin, 2013). It has been proposed that the MRN acts to inhibit the consolidation and retrieval of aversive memories through serotonergic projections to the DH (Deakin, 2013).…”

Section: Introductionmentioning

confidence: 99%