Quantitative analysis of RNAscope staining for expression in mouse brain tissue as a measure of Neuronal Activation.

The expression of mRNA is an indirect marker of neuronal activity. RNAscope ACD Bio RNAscope (now Biotechne) is a proprietary in-situ mRNA detection technology using branched DNA amplification and z paired probes to deliver a robust and specific assay designed primarily for use on formalin fixed paraffin sections [1]. In the present study we adapted this technology to be used in frozen sections to allow quantitative analysis of gene expression in different mouse brain regions during neuropharmacology studies.

Pharmacology profile of F17464, a dopamine D receptor preferential antagonist.

F17464 (N-(3-{4-[4-(8-Oxo-8H-[1,3]-dioxolo-[4,5-g]-chromen-7-yl)-butyl]-piperazin-1-yl}-phenyl)-methanesulfonamide, hydrochloride) is a new potential antipsychotic with a unique profile. The compound exhibits high affinity for the human dopamine receptor subtype 3 (hD) (K = 0.17 nM) and the serotonin receptor subtype 1a (5-HT) (K = 0.

Distinctive in vitro signal transduction profile of NLX-112, a potent and efficacious serotonin 5-HT receptor agonist.

Objectives: NLX-112 (befiradol, F13640) is a selective serotonin 5-HT receptor agonist. Although it has been tested in vivo, little has been reported on its in vitro signal transduction profile.

Methods: NLX-112 was tested on G-protein activation, inhibition of adenylyl cyclase, ERK1/2 phosphorylation (pERK) and receptor internalization in recombinant cell lines.

G-protein coupled receptor 35 (GPR35) activation and inflammatory pain: Studies on the antinociceptive effects of kynurenic acid and zaprinast.

G-protein coupled receptor 35 (GPR35) is a former "orphan receptor" expressed in brain and activated by either kynurenic acid or zaprinast. While zaprinast has been studied as a phosphodiesterase inhibitor, kynurenic acid (KYNA) is a tryptophan metabolite and has been proposed as the endogenous ligand for this receptor. In the present work, we showed that GPR35 is present in the dorsal root ganglia and in the spinal cord and in order to test the hypothesis that GPR35 activation could cause analgesia, we administered suitable doses of zaprinast or we increased the local concentration of KYNA by administering a precursor (kynurenine) or by inhibiting its disposal from the CNS (with probenecid).

Partial agonist properties of the antipsychotics SSR181507, aripiprazole and bifeprunox at dopamine D2 receptors: G protein activation and prolactin release.

Dopamine D2 receptor antagonists induce hyperprolactinemia depending on the extent of D2 receptor blockade. We compared the effects of the new antipsychotic agents SSR181507 ((3-exo)-8-benzoyl-N-[[(2 s)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl]methyl]-8-azabicyclo[3.2.

Clozapine, ziprasidone and aripiprazole but not haloperidol protect against kainic acid-induced lesion of the striatum in mice, in vivo: role of 5-HT1A receptor activation.

Excessive activation of non-NMDA receptors, AMPA and kainate, contributes to neuronal degeneration in acute and progressive pathologies, possibly including schizophrenia. Because 5-HT(1A) receptor agonists have neuroprotective properties (e.g.

Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implications for treatment of schizophrenia.

Serotonin 5-HT1A receptors are promising targets in the management of schizophrenia but little information exists about affinity and efficacy of novel antipsychotics at these sites. We addressed this issue by comparing binding affinity at 5-HT1A receptors with dopamine rD2 receptors, which are important targets for antipsychotic drug action. Agonist efficacy at 5-HT1A receptors was determined for G-protein activation and adenylyl cyclase activity.

Anticataleptic properties of alpha2 adrenergic antagonists in the crossed leg position and bar tests: differential mediation by 5-HT1A receptor activation.

Rationale: Recent studies suggest that alpha(2) adrenoceptor blockade may improve the antipsychotic-like effects of neuroleptics and attenuate dopamine D(2) receptor antagonist-induced catalepsy. However, several alpha(2) adrenergic antagonists also display serotonin 5-HT(1A) receptor agonist activity, which may contribute to anticataleptic actions.

Objectives: In this study, we examined a series of alpha(2) adrenergic antagonists to determine the role of activity at serotonin 5-HT(1A) receptors in their anticataleptic effects.

Progressive sensorimotor impairment is not associated with reduced dopamine and high energy phosphate donors in a model of ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is a genetic disease, associated with progressive motor impairment and a lack of functional ATM protein. It has been reported that immunoreactive tyrosine hydroxylase and dopamine transporter are reduced in an Atm-/- mouse model of A-T. These observations led to a hypothesis that A-T is associated with loss of nigrostriatal dopamine and prompted the launch of clinical trials to evaluate a therapeutic utility of the anti-parkinsonian drug, l-DOPA.

The PARP inhibitor benzamide protects against kainate and NMDA but not AMPA lesioning of the mouse striatum in vivo.

Overactivation of poly(ADP-ribose) polymerase (PARP) in response to genotoxic insults can cause cell death by energy deprivation. We previously reported that neurotoxic amounts of kainic acid (KA) injected into the rat striatum produce time-dependent changes in striatal PARP activity in vivo. Here, we have investigated the time-course of KA-induced toxicity and the effects of the PARP inhibitor benzamide on KA, AMPA and NMDA neurotoxicities in vivo, by measuring changes in the volume of the lesion and in NAD+ and ATP levels induced by the intra-striatal injection of these excitotoxins in C57Bl/6N mice.