Papers by Ryszard Przewlocki
Pharmaceutics, Dec 27, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Psychoneuroendocrinology, 2008
Autism is a severe behavioral disorder characterized by pervasive impairments in social interacti... more Autism is a severe behavioral disorder characterized by pervasive impairments in social interactions, deficits in verbal and non-verbal communication, and stereotyped behaviors, with a four times higher incidence in boys than in girls. The core symptoms are frequently accompanied by a spectrum of neurobehavioral and immunological derangements, including: aberrant sensitivity to sensory stimulation, anxiety, and decreased cellular immune capacity. Recently, a new potential rodent model of autism induced by prenatal exposure to valproic acid (VPA rats) has been proposed. In order to determine if gender has an influence on alterations observed in VPA rats, male and female rats have been evaluated in a battery of behavioral, immunological, and endocrinological tests. A plethora of aberrations has been found in male VPA rats: lower sensitivity to pain, increased repetitive/stereotypic-like activity, higher anxiety, decreased level of social interaction, increased basal level of corticosterone, decreased weight of the thymus, decreased splenocytes proliferative response to concanavaline A, lower IFN-gamma/IL-10 ratio, and increased production of NO by peritoneal macrophages. Female VPA rats exhibited only increased repetitive/stereotypic-like activity and decreased IFN-gamma/IL-10 ratio. Sexual dimorphism characteristics for measured parameters have been observed in both groups of animals, except social interaction in VPA rats. Our results confirm existence of similarities between the observed pattern of aberrations in VPA rats and features of disturbed behavior and immune function in autistic patients, and suggest that they are gender-specific, which is intriguing in light of disproportion in boys to girls ratio in autism.
Psychopharmacology, 2007
It has been suggested that behavioral aberrations observed in autism could be the result of dysfu... more It has been suggested that behavioral aberrations observed in autism could be the result of dysfunction of the neuroregulatory role performed by the endogenous opioid peptides. Many of those aberrations have been recently modeled in rats exposed to valproic acid (VPA) on the 12th day of gestation (VPA rats).
Neuropharmacology, 2019
Exposure to drug-associated cues evokes drug-craving and upregulates noradrenaline (NA) and dopam... more Exposure to drug-associated cues evokes drug-craving and upregulates noradrenaline (NA) and dopamine (DA) system activity. Importantly, conditional stimulus-induced drug-seeking behavior depends particularly on phasic DA signaling downstream from the ventral tegmental area (VTA), a midbrain structure key for the regulation of cocaine seeking. In particular, the activity of the alpha 1-adrenergic receptor (α 1-AR), which has recently been hypothesized to modulate salience encoding, is capable of bidirectional regulation of VTA dopaminergic activity. Thus, the impact of the conditional stimuli (CSs) on drug-seeking behavior might involve α 1-AR signaling in the VTA. To date, the role of VTA α 1-ARs in regulating CSinduced cocaine seeking has not been studied. In male Sprague-Dawley rats, we found that intra-VTA terazosin, a selective α 1-AR antagonist, attenuated CS-induced cocaine seeking in a novel context and under extinction conditions, as well as CS-induced reinstatement of cocaine seeking. In contrast, terazosin microinfusion in a dose that attenuated CS-induced cocaine seeking had no effects on CS-induced food seeking or stress (2 mg/kg yohimbine)evoked reinstatement of cocaine seeking. The potential nonspecific effects (sedative, anxiogenic) of α 1-AR blockade of the VTA were also measured in the open-field test. Finally, using immunostaining, we demonstrated dopamine β-hydroxylase (DBH)-positive afferents in the VTA of cocaine-abstinent rats, providing a neuroanatomical substrate for the α 1-AR mechanism. These results demonstrated for the first time that NAergic signaling via VTA α 1-ARs potently and selectively regulates CS-induced cocaine seeking. Our findings provide new neuronal mechanisms that regulate cocaine craving.
Additional file 1. Lists of regulated genes. The complete list of genes regulated by dexamethason... more Additional file 1. Lists of regulated genes. The complete list of genes regulated by dexamethasone, aldosterone, progesterone, dihydrotestosterone and estradiol. The list includes p values, corrected p values and log2 ratios for all pairwise comparisons.
The lists of transcript IDs and gene names corresponding to Venn diagrams for the hippocampus and... more The lists of transcript IDs and gene names corresponding to Venn diagrams for the hippocampus and striatum are presented in the first and second sheet respectively. Column names indicate which drugs alter the expression of listed transcripts. In case where only one substance name is listed, the altered expression level is drug-specific (at p 0.3 at least at one of the time points in the analyzed tissue). (XLSX 12 kb)
The table summarizing results of gene expression profiling of ketamine effects in the mouse stria... more The table summarizing results of gene expression profiling of ketamine effects in the mouse striatum using RNA-seq (n = 4). In the first sheet 23 genes regulated by ketamine selected from the microarray profiling are listed with their chromosome location, fold change over control, p-value and FDR. The second sheet presents a list of the 15 selected genes with significant differences in expression between ketamine-treated and saline controls (p
The lists of probe IDs and gene names obtained in the comparison between tissues based on two-way... more The lists of probe IDs and gene names obtained in the comparison between tissues based on two-way ANOVA results (at p 0.3 at least at one of the time points). Transcripts regulated by drug treatment in the hippocampus or striatum specifically and a list of genes altered in both tissues are presented. (XLSX 10 kb)
Acta Neurobiologiae Experimentalis, 2007
Pain, 2005
The nociceptin system seems to be involved in modulation of acute nociceptive stimulation and in ... more The nociceptin system seems to be involved in modulation of acute nociceptive stimulation and in chronic pain processes, e.g. inflammation and neuropathy. In the present study, we examined the analgesic effect of a new opioid receptor-like (ORL1) receptor agonist, Ro64-6198, and compared it with the effect of endogenous ORL1 receptor agonist, nociceptin/orphanin FQ (N/OFQ), in a model of neuropathic pain in the rat. Ro64-6198 was injected intrathecaly (i.t.), intraplantarly (i.pl.) and subcutaneously (s.c.), and responses of neuropathic rats were measured in tactile (von Frey) and thermal (cold water) allodynia tests. Ro64-6198 did not change the pain threshold in naive animals, but exhibited antiallodynic activity in neuropathic rats. This effect was observed after i.t. and i.pl. but not after s.c. administration. Moreover, the observed antiallodynic potency of Ro64-6198 was weaker in comparison with N/OFQ after i.t. administration of either agonist, but almost equal after i.pl. injection. Selective antagonists of the ORL1 receptor, [Phe 1 J(CH 2-NH)Gly 2 ]NC(1-13)NH 2 (PheJ) and [N-Phe 1 ]-NC(1-13)NH 2 (NPhe), inhibited the antiallodynic actions of Ro64-6198 which indicated that the spinal and peripheral antinociceptive effects were mediated by ORL1 receptors. Therefore, besides spinal, also peripheral ORL1 receptors may be targeted by drugs designed for the long-term treatment of chronic pain.
Genes, Brain and Behavior, 2012
The molecular alterations that underlie the long-lasting behavioural effects of drugs of abuse, s... more The molecular alterations that underlie the long-lasting behavioural effects of drugs of abuse, such as psychomotor sensitization and physical dependence, are still not known. Moreover, it is not known which molecular effects are similar for addictive drugs from various pharmacological classes. In this study, we utilized wholegenome microarray profiling to evaluate the detailed time-course of transcriptional alterations in the mouse striatum during chronic treatment with heroin (HER) and methamphetamine (METH) and after period of spontaneous withdrawal. We identified 27 genes regulated by chronic drug administration. The overlap between lists of HER-and METH-induced genes was highly significant. The most substantial impact on the gene expression profile was observed for circadian genes (Per1, Per2 and Nr1d1). However, changing the treatment scheme from diurnal to nocturnal was sufficient to attenuate the drug-induced changes in circadian gene mRNA levels. Both of the drugs caused a dose-dependent induction in glucocorticoid-dependent genes with relatively long mRNA half-lives (Fkbp5, Sult1a1 and Plin4). The analysis also showed a drug-regulated group of transcripts enriched in the nucleus accumbens and includes well known (Pdyn, Cartpt and Rgs2) as well as new (Fam40b and Inmt) candidate genes. All identified alterations in the striatal transcriptome were transient and persisted up to 6 days after withdrawal. Behavioural sensitization, however, was maintained throughout the 12-day withdrawal period for both HER and METH. We suggest that transient gene expression alterations during drug treatment and in the early period of withdrawal are involved in the establishment of persistent neuroplastic alterations responsible for the development of drug addiction.
Wszechświat, Mar 31, 2017
European Neuropsychopharmacology, 2021
Clusters of genes co-expressed with (1) , (2) (), and (3) after morphine treatment (SAL, control ... more Clusters of genes co-expressed with (1) , (2) (), and (3) after morphine treatment (SAL, control group; MOR, acute [ACU] and chronic [CHR] morphine groups). Colored rectangles represent expression levels of the gene indicated by the probe set on the left and gene symbol on the right. Intensity of the color is proportional to the fold change as indicated on the bar below the cluster image. Network graphs of transcripts co-regulated with (1) , (2) (), and (3) were generated using the gene-to-gene correlation tool in WebQTL (Hippocampus Consortium M430v2 Dec05 PDNN). Correlation coefficients for each pair of transcripts are indicated beside the line. The gene was represented by three different probe sets on the microarray. Confirmation of morphine induced regulation of expression of three selected genes by quantitative real-time reverse transcription polymerase chain reaction (qPCR). Results are presented as fold change over control group with standard error (= 6 to 9). Significant mai...
Acutely treated mice (= 9) were injected with a single dose of morphine (20 mg/kg, subcutaneously... more Acutely treated mice (= 9) were injected with a single dose of morphine (20 mg/kg, subcutaneously). Chronically treated animals (= 9) were injected with increasing doses of morphine for 5 days (10, 20, and 40 mg/kg, subcutaneously; see Materials and methods). Control (= 9) and acute morphine groups received injections of saline in the same time schedule as the chronic group received morphine. Animals were killed by decapitation 4 hours after the last injection. The time point used for tissue collection and gene expression analysis is indicated by the red arrow.<b>Copyright information:</b>Taken from "Morphine effects on striatal transcriptome in mice"http://genomebiology.com/2007/8/6/R128Genome Biology 2007;8(6):R128-R128.Published online 28 Jun 2007PMCID:PMC2394777.
<b>Copyright information:</b>Taken from "Gene expression profiling in the striat... more <b>Copyright information:</b>Taken from "Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes"BMC Genomics 2006;7():146-146.Published online 13 Jun 2006PMCID:PMC1553451.nbred mouse strains were performed using strategy described by the scheme. Five independent biological replicates of microarray were prepared for each strain of mice. Total RNA isolated from the striatum of three animals was pooled. Each pool of total RNA was separately converted to cRNA and hybridized to a single microarray. Samples from two separate groups of animals from each strain of mice were used in qPCR experiment.
Hormones, Brain and Behavior, 2017
The state-of-the-art regarding the important role that endogenous opioid peptides and their respe... more The state-of-the-art regarding the important role that endogenous opioid peptides and their respective receptors play in the regulation of a variety of physiological and behavioral functions under normal and stressful conditions is presented. This chapter covers the biology, pharmacology, and molecular biology of opioids, as well as the implication of opioids in stress-related pathology.
Background Depression is the most prevalent neuropsychiatric disorder among post-stroke patients.... more Background Depression is the most prevalent neuropsychiatric disorder among post-stroke patients.Depressive symptoms can be observed already in the first few days following the stroke onset.The aim of this research was to identify specific factors or groups of factors that contribute to the occurrence of depressive symptoms among patients in the acute phase after ischemic stroke. Methods and findings The experimental group consisted of 95 patients after ischemic stroke. The inclusion criteria were strictly specified diagnostic criteria encompassing neuroimaging procedures CT and MRI, physical and neurological examination.The experimental procedure involved neuropsychological cognitive assessment (MMSE, The Clock Drawing Test, selected experimental methods from the AAAAÂÂÂÂAÂÂÂÂAAÂÂÂÂAÂÂÂ
ÂAAAÂÂÂÂAÂÂÂÂAAÂÂÂÂAÂÂÂucki Book), observations, and questionnaires for mood disorders (BDI, HDRS). Depressive symptoms were observed among 57%-69% of the patients in the acute phase ...
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Papers by Ryszard Przewlocki