The CRF/Urocortin systems as therapeutic targets for alcohol use disorders.

Development and maintenance of alcohol use disorders have been proposed to recruit critical mechanisms involving Corticotropin Releasing Factor and Urocortins (CRF/Ucns). The CRF/Ucns system is comprised of a family of peptides (CRF, Ucn 1, Ucn 2, Ucn 3) which act upon two receptor subtypes, CRFR1 and CRFR2, each with different affinity profiles to the endogenous peptides and differential brain distribution. Activity of CRF/Ucn system is further modulated by CRF binding protein (CRF-BP), which regulates availability of CRF and Ucns to exert their actions.

Maternal Separation Stress Affects Voluntary Ethanol Intake in a Sex Dependent Manner.

Maternal separation (MS) stress is a predictive animal model for evaluating the effects of early stress exposure on alcohol use disorders (AUD). The extended amygdala (AMY) is a complex circuit involved in both stress- and ethanol-related responses. We hypothesized that MS stress may increase ethanol consumption in adulthood, as well as augment neuronal activity in extended AMY, in a sex-dependent manner.

Involvement of the ventral, but not dorsal, hippocampus in anxiety-like behaviors in mice exposed to the elevated plus maze: participation of CRF1 receptor and PKA pathway.

Background: The hippocampus is a limbic structure involved in anxiety-like behaviors. We aimed to evaluate the role of the dorsal (DH) and ventral (VH) hippocampus in anxiety-like behaviors in the elevated plus maze (EPM).

Methods: We inhibited these brain regions using cobalt chloride (CoCl: 1.

Tonic modulation of anxiety-like behavior by corticotropin-releasing factor (CRF) type 1 receptor (CRF1) within the medial prefrontal cortex (mPFC) in male mice: role of protein kinase A (PKA).

The medial prefrontal cortex (mPFC) and the neuropeptide corticotropin-releasing factor (CRF) have recently been receiving more attention from those interested in the neurobiology of anxiety. Here, we investigated the CRF pathway in the modulation of anxiety-like behaviors in male mice exposed to the elevated plus-maze (EPM), through intra-mPFC injections of CRF, CP376395 [N-(1-ethylpropyl)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-4-pyridinamine hydrochloride, a CRF type 1 receptor antagonist (CR F1)] or H-89 [N-[2-[[3-(4-bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide dihydrochloride, a protein kinase (PKA) inhibitor]. We also investigated the effects of intra-mPFC injections of H-89 on the behavioral effects induced by CRF.

Ethopharmacological evaluation of the rat exposure test: a prey-predator interaction test.

The rat exposure test (RET) is a prey (mouse)-predator (rat) situation that activates brain defensive areas and elicits hormonal and defensive behavior in the mouse. Here, we investigated possible correlations between the spatiotemporal [time spent in protected (home chamber and tunnel) and unprotected (surface) compartments and frequency of entries into the three compartments] and ethological [e.g.

Corticosterone does not change open elevated plus maze-induced antinociception in mice.

It has been demonstrated that the exposure of rodents to the standard elevated plus-maze (sEPM: 2 open and 2 enclosed arms) elicits defensive behavioral reactions and antinociception and also activates the hypothalamo-pituitary-adrenal (HPA) axis. We have recently reported that EPM-induced antinociception is particularly observed when rats and mice are exposed to a totally open EPM (oEPM: 4 open arms). Given that the oEPM seems to be a more aversive situation than the sEPM, we hypothesized that oEPM exposure would induce higher plasma levels of corticosterone than sEPM exposure in mice.

Anxiogenic and antinociceptive effects induced by corticotropin-releasing factor (CRF) injections into the periaqueductal gray are modulated by CRF1 receptor in mice.

Chemical or electrical stimulation of the dorsal portion of the midbrain periaqueductal gray (dPAG) produces anxiogenic and antinociceptive effects. In rats, chemical stimulation of dPAG by local infusion of the neuropeptide corticotropin-releasing factor (CRF) provokes anxiogenic effects in the elevated plus-maze test (EPM). CRF also produces antinociception when injected intracerebroventricularly in rats, however it remains unclear whether this response is also observed following CRF injection into the dPAG in mice.

Anxiogenic-like effects induced by NMDA receptor activation are prevented by inhibition of neuronal nitric oxide synthase in the periaqueductal gray in mice.

Glutamate-NMDA (N-methyl-D-aspartate) receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction. We have recently demonstrated that the vigorous defensive-like behaviors (e.g.

Defensive-like behaviors and antinociception induced by NMDA injection into the periaqueductal gray of mice depend on nitric oxide synthesis.

Glutamate NMDA receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction. Considering that NMDA receptor triggers activation of neuronal nitric oxide synthase (nNOS), enzyme that produces nitric oxide (NO), this study investigated the effects of intra-PAG infusions of NPLA (Nomega-propyl-L-arginine), an nNOS inhibitor, on behavioral and antinociceptive responses induced by local injection of NMDA receptor agonist in mice. The behaviors measured were frequency of jumping and rearing as well as duration (in seconds) of running and freezing.