Exploratory behaviour of rats in the elevated plus-maze is differentially sensitive to inactivation of the basolateral and central amygdaloid nuclei

Moreira, Carolina Campos Lima; Masson, Sueli; Carvalho, Milene Cristina de; Brandão, Marcus Lira

doi:10.1016/j.brainresbull.2006.10.004

Cited by 78 publications

(56 citation statements)

References 63 publications

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“…The behavioral effects of MAP4343 correlated with rescue of the alterations induced by isolation-rearing in α-tubulin isoforms and microtubule dynamics in the hippocampus, amygdala, and PFC. The three brain areas examined are important in all of the behavioral tests used (23)(24)(25) and have been shown to differently respond to stress in terms of alterations in dendritic structure (26). It is possible to speculate that the different effects on microtubule dynamics induced by MAP4343 in the three brain regions are associated with restoration of neuronal integrity and physiological behavioral patterns.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental design. Briefly, male SD rats (postnatal day [21][22][23][24][25] were housed in groups of four per cage (grouped, n = 16) or singly housed (isolated, n = 48) for 40 d. Thereafter, the animals started receiving daily (once a day) injections of treatments as follow: (i) Grouped+Vehicle (control; n = 16); (ii) Isolated+ Vehicle (n = 16); (iii) Isolated+MAP4343 (10 mg/kg; n = 16) and (iv) Isolated+Fluoxetine (10 mg/kg; n = 16). To study the effects of the drugs in relation to the duration of treatments, the animals were split in two cohorts (n = 8 per each treatment group), namely the acute phase cohort with behavioral assays performed between days 1 and 4 of treatment (treatment injection received before behavioral testing), and the subchronic phase cohort with behavioral assays performed between days 7 and 10 of treatment (treatment injection received after behavioral testing).…”

Section: β-Methoxy-pregnenolone (Map4343) As An Innovative Therapeutmentioning

confidence: 99%

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3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

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

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Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in α-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term treatment explaining their delayed therapeutic efficacy. The microtubule associated protein type-2 (MAP-2) modulates neuronal microtubule dynamics. Our hypothesis is that MAP-2 represents an innovative target for the treatment of DDs. The synthetic pregnenolone-derivative MAP4343 (3β-methoxy-pregnenolone) binds MAP-2 in vitro and increases its ability to stimulate tubulin assembly. Here, we show that MAP4343 has antidepressant efficacy in rats and advantages compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. A single injection of MAP4343 changes the expression of α-tubulin isoforms indicative of increased microtubule dynamics in the hippocampus of naïve Sprague–Dawley rats, whereas fluoxetine had no effects. MAP4343 has positive efficacy in the rat forced swimming test (FST), the most used assay to screen potential antidepressant drugs by decreasing immobility behavior. In the rat isolation-rearing model of depression, administration of MAP4343 showed more rapid and more persistent efficacy compared with fluoxetine in recovering “depressive-like” behaviors. These effects were accompanied by modifications of α-tubulin isoforms in the hippocampus, amygdala, and prefrontal cortex. Our findings suggest the potential therapeutic use of MAP4343 for the treatment of DDs, based on a unique mechanism of action.

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Section: Discussionmentioning

confidence: 99%

Section: β-Methoxy-pregnenolone (Map4343) As An Innovative Therapeutmentioning

confidence: 99%

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

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

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“…Interestingly, microinjections of muscimol into the ACe have been shown to result in an 'anxiolytic-like' response in the social interaction and elevated plus maze tests (Sanders and Shekhar, 1995;Moreira et al, 2007). Thus, it is possible that the muscimol microinfusions had an 'anxiolytic-like' effect and this decreased amphetamine self-administration in HR rats.…”

Section: Discussionmentioning

confidence: 99%

Individual Differences in Amphetamine Self-Administration: The Role of the Central Nucleus of the Amygdala

Cain

Denehy

Bardo

2007

Neuropsychopharmacol

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Rats categorized as high responder (HR), based on their activity in an inescapable novel environment, self-administer more amphetamine than low responder (LR) rats. The current study examined if the central nucleus of the amygdala (ACe) contributes to the elevated response for amphetamine in HR rats. Male Sprague-Dawley rats were classified as HR and LR rats based on their activity in inescapable novelty and novelty place preference, and then were trained to self-administer amphetamine (0.1 mg/kg/infusion). Once stable responding was achieved, rats received microinfusions of the GABA A agonist muscimol (0.5 mg/0.5 ml) or phosphate-buffered saline into the ACe immediately before self-administration of amphetamine (0.1, 0.03, 0.01, or 0.001 mg/kg/infusion) or saline. An additional group of rats was trained to lever press for sucrose rather than amphetamine. Based on the inescapable novelty test, HR rats self-administered more amphetamine than LR rats at the 0.03 and 0.01 mg/kg/infusion unit doses; there were no significant individual differences in amphetamine self-administration based on the novelty place preference test. Inactivation of the ACe with muscimol decreased selfadministration at the 0.03 and 0.01 mg/kg/infusion unit doses in HR rats, but had no effect on LR rats. ACe inactivation had no reliable effect on inactive lever responding and appeared to be region specific based on anatomical controls. In addition, while inactivation of the ACe decreased responding for sucrose, inactivation did not differentially affect HR and LR rats. These results suggest that the ACe contributes to the elevated rate of amphetamine self-administration in HR rats.

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“…Animal studies suggest that changes in BLA and CeA activity can alter state anxiety [9; also see Section 3.2.]. However, most investigations have focused on the BLA with the exact role of the CeA remaining ill-defined [for example, see 84,85], although it appears that BLA to CeA circuitry can directly regulate anxiety-like behavior as measured on the elevated plus maze [EPM,86]. This direct control is thought to result from BLA excitation of GABAergic neurons in the lateral CeA to induce feed-forward inhibition of output from the medial CeA [86], similar to that induced by BLA excitation of ITC cells during fear extinction.…”

Section: Amygdala Reactivity In Anxiety Disordersmentioning

confidence: 99%

“…Although contradictory results exist on the role of benzodiazepines in the BLA versus CeA, particularly when animals are tested on the EPM [9,84,224] have suggested that distinct benzodiazepine receptor subtypes located within subregions of the amygdala may differentially alter avoidance responses to "potential threat" (EPM and BLA) versus "discrete, unambiguous threat" (shock probe burying and CeA).…”

Section: Evidence Delineating Effects Of Anxiolytic Drugs On Amygdalamentioning

confidence: 99%

The Role of the Amygdala in Anxiety Disorders

Forster¹,

Novick²,

Scholl³

et al. 2012

The Amygdala - A Discrete Multitasking Manager

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Exploratory behaviour of rats in the elevated plus-maze is differentially sensitive to inactivation of the basolateral and central amygdaloid nuclei

Cited by 78 publications

References 63 publications

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Individual Differences in Amphetamine Self-Administration: The Role of the Central Nucleus of the Amygdala

The Role of the Amygdala in Anxiety Disorders

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