Antidepressant-like effects of the glucocorticoid receptor antagonist RU-43044 are associated with changes in prefrontal dopamine in mouse models of depression

Ago, Yukio; Arikawa, Shinsuke; Yata, Miyuki; Yano, Koji; Abe, Michikazu; Takuma, Kazuhiro; Matsuda, Takehisa

doi:10.1016/j.neuropharm.2008.08.026

Cited by 93 publications

(66 citation statements)

References 70 publications

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“…Previous studies investigating the effects of systemic administration of corticosterone on DA efflux in the mPFC have produced conflicting results. Administration of corticosterone via drinking water or s.c. injections increased, decreased, or had no effect on DA efflux (14,(18)(19)(20)(21). The present study used reverse microdialysis to administer drugs locally into different brain regions.…”

Section: Discussionmentioning

confidence: 82%

Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function

Butts¹,

Weinberg

Young³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

156

123

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Enhanced dopamine efflux in the prefrontal cortex is a well-documented response to acute stress. However, the underlying mechanism(s) for this response is unknown. Using in vivo microdialysis, we demonstrate that blocking glucocorticoid receptors locally within the rat prefrontal cortex results in a reduction in stress-evoked dopamine efflux. In contrast, blocking glucocorticoid receptors in the ventral tegmental area did not affect stress-evoked dopamine efflux in the prefrontal cortex. Additionally, local administration of corticosterone into the prefrontal cortex increased prefrontal dopamine efflux. The functional impact of enhanced dopamine efflux evoked by acute stress was demonstrated using a cognitive task dependent on the prefrontal cortex and sensitive to impairment in working memory. Notably, stress-induced impairments in cognition were attenuated by blockade of glucocorticoid receptors in the prefrontal cortex. Taken together, these data demonstrate that glucocorticoids act locally within the prefrontal cortex to modulate mesocortical dopamine efflux leading to the cognitive impairments observed during acute stress.

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Section: Discussionmentioning

confidence: 82%

Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function

Butts¹,

Weinberg

Young³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

156

123

View full text Add to dashboard Cite

show abstract

“…Postoperative analgesia was a single injection of buprenorphine (0.1 mg/kg, i.p. ; Ago et al, 2008Ago et al, , 2011. The active probe membranes were 3-and 1-mm long in the prefrontal cortex and nucleus accumbens, respectively.…”

Section: In Vivo Microdialysismentioning

confidence: 99%

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Ago

Araki

Tanaka

et al. 2013

Neuropsychopharmacol

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Isolation-reared male rodents show abnormal behaviors such as hyperlocomotion, aggressive behaviors, deficits of prepulse inhibition, and depression-and anxiety-like behaviors, but the neurochemical mechanism for the effects of psychological stress in these animals is not fully understood. This study examined the effects of social interactions between isolation-reared mice and intruder mice on brain monoaminergic systems. A cage was divided into two compartments by a mesh partition to prevent direct physical interactions. The 20-min encounter with an intruder elicited a restless and hyperexcitable state (hyperactivity) in male, but not in female, isolationreared mice, whereas encounters with a sleeping intruder or a novel object did not. Although the encounter did not affect prefrontal neuronal-activity-marker c-Fos expression, dopamine (DA) levels, or serotonin (5-HT) levels in male group-reared mice or female isolation-reared mice, it increased prefrontal c-Fos expression, DA levels, and 5-HT levels in male isolation-reared mice. Furthermore, encounter-induced increases in c-Fos expression in the dorsal raphe nucleus and ventral tegmental area, but not in the nucleus accumbens shell, were much greater in isolation-reared than group-reared male mice. A 5-HT 1A receptor agonist, a metabotropic glutamate 2/3 receptor agonist, and a gamma-aminobutyric acid A receptor agonist attenuated isolation-induced aggressive behaviors and encounter-induced hyperactivity, c-Fos expression in the prefrontal cortex and dorsal raphe nucleus, and increases in prefrontal 5-HT levels. These findings suggest that the prefrontal DA and 5-HT systems are activated by encounter stimulation in male isolationreared mice, and the encounter-induced activation of 5-HT system triggers the induction of some abnormal behaviors in male isolation-reared mice. Furthermore, this study implies that the encounter stimulation-induced signal has a pharmacological significance.

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“…17,65,67,81,93) We also found that isolation rearing increased immobility time in the forced swim test in mice. 110) Animal models of repeated stress exposure simulate the presumed etiology of depression, and this stress may be produced by exogenous corticosterone administration. [111][112][113][114] Thus, chronic corticosterone administration, like isolation rearing, 110) provides a reliable rodent model of depression for studies on the neurobiological mechanisms of depression or antidepressant-like effects.…”

Section: Corticosterone Modelmentioning

confidence: 99%

“…110) Animal models of repeated stress exposure simulate the presumed etiology of depression, and this stress may be produced by exogenous corticosterone administration. [111][112][113][114] Thus, chronic corticosterone administration, like isolation rearing, 110) provides a reliable rodent model of depression for studies on the neurobiological mechanisms of depression or antidepressant-like effects. We found that chronic corticosterone administration and isolation rearing increased immobility time in the forced swim and tail suspension tests in mice, and that the glucocorticoid receptor antagonist RU-43044 reversed the increased immobility time in the forced swim test.…”

Section: Corticosterone Modelmentioning

confidence: 99%

Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan

Matsuda

2013

Biological & Pharmaceutical Bulletin

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Alterations in serotonin (5-HT) neurochemistry have been implicated in the etiology of major neuropsychiatric disorders such as anxiety-spectrum disorders, depression, and schizophrenia. The neuromodulatory effects of 5-HT are mediated through 14 receptor subtypes, and those receptors, including the 5-HT 1A receptor, are considered to be potential targets for the treatment of psychiatric disorders. We developed the novel 5-HT 1A receptor agonist MKC-242 (called osemozotan) and characterized its neurochemical and pharmacological profiles. 5-HT 1A receptor agonists modulate the release of amine neurotransmitters through the activation of presynaptic or postsynaptic 5-HT 1A receptors in the brain. The agonist has antianxiety and antidepressant effects and improves abnormal behaviors such as aggressive behavior and deficits of prepulse inhibition in isolation-reared mice. We also demonstrated that spinal 5-HT 1A receptor activation is involved in isolation rearing-induced hypoalgesia. Concerning the mechanism for induction of isolation-induced abnormal behaviors, we have recently found that the raphe-prefrontal 5-HT system plays a key role in encounter stimulation-induced hyperactivity in isolation-reared mice. Furthermore, we showed that osemozotan attenuates psychostimulant-induced behavioral sensitization and that prefrontal dopamine release is enhanced by functional interaction between the 5-HT 1A receptor and other receptors. This review summarizes the neuropharmacology of the 5-HT 1A receptor, focusing on our studies using osemozotan, and suggests that the 5-HT 1A receptor may be a target molecule for the treatment of psychiatric disorders, pain, and drug dependence.

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Antidepressant-like effects of the glucocorticoid receptor antagonist RU-43044 are associated with changes in prefrontal dopamine in mouse models of depression

Cited by 93 publications

References 70 publications

Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function

Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function

Role of Social Encounter-Induced Activation of Prefrontal Serotonergic Systems in the Abnormal Behaviors of Isolation-Reared Mice

Neuropharmacologic Studies on the Brain Serotonin<sub>1A</sub> Receptor Using the Selective Agonist Osemozotan

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