The mPFC showed an early phase of gating which may later be modulated by CA3 and DG activity. Furthermore, cannabinoid receptor activation disrupted auditory gating in CA3, DG and mPFC, an effect which was prevented by CBI receptor antagonism. The results further demonstrate the presence of a non-gating rat population which responded differently

to cannabinoid agonists. (C) 2008 Elsevier Ltd. All rights reserved.”
“The present Study was conducted to determine whether the activation of neurokinin-1 receptor (NK-1R) by its agonist (GR73632) enhances the capsaicin-evoked Substance P (SP) release using a radioimmunoassay. A pre-exposure to GR73632 enhanced the capsaicin-evoked SP release in a time- and dose-dependent manner. The augmentation of capsaicin-evoked SP release by GR73632 was completely Bindarit solubility dmso inhibited by pharmacological blockade of NK-1R or transient receptor potential vanilloid receptor subtype I (TRPV1), and was partially attenuated by the inhibition of either protein kinase C (PKC), cyclooxygenase (COX) or phospholipase C (PLC), p38 or p42/44 mitogen-activated protein (MAP) kinase, but not protein kinase A.

This augmentation of SP release was further increased MRT67307 concentration by inhibition of c-Jun NH(2)-terminal kinase. A short-term (10 min) exposure to GR73632 resulted in an increase in the TRPV1 phosphorylation. The increase in the TRPV1 phosphorylated forms induced by a 60-min exposure to GR73632 was completely abolished by the inhibition of either PKC, COX or PLC, p38 or p42/44 MAP kinases.

Immunocytochemistry study demonstrated that the NK-1R see more and TRPV1 were mainly co-expressed in the small-sized neurons. These findings suggest that the activation of NK-1R by its agonist, by sensitizing the TRPV1 through the PKC phosphorylation of TRPV1, may play a role in the enhancement of the capsaicin-evoked SP release from Cultured rat DRG neurons. (C) 2008 Elsevier Ltd. All rights reserved.”
“To date, nothing is known of the pharmacological properties of isomers of domoic acid (DA) in vivo in mammals. Here we assessed the acute seizurogenic and toxic properties of DA, isodomoic acids A, B and C (Iso-A, -B, -C), and the therapeutic potential of these compounds as pharmacological preconditioning agents. DA, Iso-A, Iso-B, and Iso-C all produced significant dose-dependent increases in seizure activity following intrahippocampal administration; doses producing half maximal cumulative seizure scores (ED(50)) were 137 pmol, 171 pmol, 13,000 pmol. and 3150 pmol, respectively. Pharmacological preconditioning with low-dose DA or Iso-A, 60 min before a high test dose of DA produced a significant reduction in seizure scores. In contrast, Iso-B and Iso-C each failed to induce any detectable tolerance to high-dose DA. Radioligand binding indicated a significant correlation between seizurogenic potency and kainate receptor affinity with K(1)s of 2.4 nM, 4.4 nM, 4990 nM and 170 nM for DA, Iso-A, Iso-B and Iso-C, respectively.