The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Selvamani, Amutha; Lincoln, Christi; Uphouse, Lynda

doi:10.1016/j.bbr.2007.01.015

Cited by 3 publications

(2 citation statements)

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“…The lordosis-inhibitory effect of 5-HT 1A receptors appear to include inhibition of cAMP-mediated events (Uphouse et al, 2000); and the ability of a 5-HT 2 receptor agonist to attenuate 5-HT 1A receptor-mediated lordosis inhibition is attenuated by inhibition of PKC (Selvamani et al, 2007). Effects of progesterone and/or its metabolite, allopregnanolone, modulate these same signaling events.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint II. Role of progesterone metabolites

Miryala¹,

Hassell²,

Adams³

et al. 2011

Hormones and Behavior

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When ovariectomized Fischer female rats are hormonally primed with 10 μg estradiol benzoate, a 5 min restraint experience rapidly inhibits lordosis behavior. Addition of progesterone to the hormonal priming prevents this restraint-induced inhibition. In prior work, we reported evidence that progesterone receptors (PR) may contribute to this protective effect of progesterone. In the current manuscript, we provide evidence that progesterone metabolites may also contribute to progesterone’s ability to reduce the effects of restraint. Ovariectomized female rats were hormonally primed with 10 μg estradiol benzoate followed 2 days later with 4.0 mg/kg of the progesterone metabolite, allopregnanolone. Allopregnanolone, administered either 4 hr or 2 hr before the restraint experience, was as effective as progesterone in reducing the lordosis-inhibitory effects of restraint. In the second experiment, progesterone metabolism was blocked with 50 mg/kg of the 5α-reductase inhibitor, finasteride. Surprisingly, finasteride did not prevent progesterone from reducing the effects of restraint. In a third experiment, we tested the possibility that allopregnanolone acted through metabolism to dihydroprogesterone. Rats were treated with allopregnanolone or with allopregnanolone plus the 3α-hydroxysteroid dehydrogenase inhibitor, indomethacin. Indomethacin did not prevent allopregnanolone from reducing the effects of restraint. Mechanisms are discussed whereby cross-talk between PR-mediated and metabolite-mediated events may converge in producing progesterone’s attenuation of the effect of restraint.

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Section: Discussionmentioning

confidence: 99%

Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint II. Role of progesterone metabolites

Miryala¹,

Hassell²,

Adams³

et al. 2011

Hormones and Behavior

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“…The vehicle for the MEK inhibitors was 30% DMSO/water. Doses and time course for all inhibitors were based on observations from pilot experiments and previous reports (Bourtchouladze et al 1998; Schafe et al 1999, 2000; Lu et al 2001; Sananbenesi et al 2003; Selvamani et al 2007). ICV infusions were by gravity after which the injector remained in place for 1 min before removal.…”

Section: Methodsmentioning

confidence: 99%

The role of PKC signaling in CRF-induced modulation of startle

et al. 2013

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Rationale Hypersignaling of corticotropin releasing factor (CRF) has been implicated in stress disorders, however many of its downstream mechanisms of action remain unclear. In vitro, CRF1 receptor activation initiates multiple cell signaling cascades, including protein kinase A (PKA), protein kinase C (PKC) and mitogen-activated protein kinase kinase MEK1/2 signaling. It is unclear however, which of these signaling cascades mediate CRF-induced behaviors during stress. Objectives We examined the role of PKA, PKC and MEK1/2 signaling pathways in CRF-induced anxiety as measured by startle hyperreactivity. Methods Mice treated with intracerbroventricular (ICV) ovine CRF (oCRF) were pretreated with the PKA inhibitor Rp-cAMPS, PKC inhibitor BIM (bisindolylmaleimide) or MEK1/2 inhibitor PD98059 (ICV) and assessed for acoustic startle reactivity. Results The PKC inhibitor BIM significantly attenuated CRF-induced increases in startle. BIM was also able to block startle increases induced by oCRF when both compounds were infused directly into the bed nucleus of stria terminalis (BNST). PKA and MEK1/2 inhibition had no significant effects on CRF-induced changes in startle at the dose ranges tested. CRF-induced disruption of PPI was not significantly reversed by any of the 3 pretreatments at the dose ranges tested. Conclusions PKC signaling is required for CRF-induced increases in startle, and this effect is mediated at least in part at the BNST. These findings suggest PKC signaling cascades: 1) may be important for the acute effects of CRF to induce startle hyperreactivity, and 2) support further research of the role of PKC signaling in startle abnormalities relevant to disorders such as posttraumatic stress disorder.

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Serotonin receptor involvement in effects of restraint on female rat lordosis behavior

Uphouse

Hiegel

Perez

et al. 2007

Pharmacology Biochemistry and Behavior

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Ovariectomized Fischer (CDF-344) rats, with bilateral cannulae in the mediobasal hypothalamus (MBH) near the ventromedial nucleus of the hypothalamus (VMN), were used to test the hypothesis that serotonin receptors in the VMN contribute to the lordosis-inhibiting effects of mild restraint. Rats were hormonally primed with 10 microg estradiol benzoate (EB) followed 48 h later with sesame seed oil. Four to six hours later (during the dark portion of the light-dark cycle), rats were pretested for sexual behavior. Thereafter, they were infused with saline, 2 microg of the serotonin (5-HT) 2 receptor agonist, (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI), or 1 microg of the 5-HT(1A) receptor antagonist, N-{2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635). After a 5 min restraint, rats were tested for sexual receptivity. Rats infused with saline showed a significant decline in lordosis behavior after restraint. Infusion with either DOI or WAY100635 attenuated these effects of restraint. These findings extend earlier observations that the lordosis-disruptive effects of mild restraint include activation of 5-HT(1A) receptors in the VMN and are the first to implicate VMN 5-HT(2) receptors in protection against mild restraint.

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The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Cited by 3 publications

References 42 publications

Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint II. Role of progesterone metabolites

Mechanisms responsible for progesterone's protection against lordosis-inhibiting effects of restraint II. Role of progesterone metabolites

The role of PKC signaling in CRF-induced modulation of startle

Serotonin receptor involvement in effects of restraint on female rat lordosis behavior

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