Przemyslaw Bienkowski

Institute of Psychiatry and Neurology, Warszawa, Masovian Voivodeship, Poland

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Publications (111)260.79 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: As in the case of cardiovascular and metabolic diseases, the prevalence of pelvic organ prolapse (POP) has been rising with the increasing proportion of elderly women in the population. The purpose of the present cross-sectional study was to evaluate the components of metabolic syndrome (MS) in urogynecological patients with a variable POP severity.
    International Urogynecology Journal 07/2014; · 2.17 Impact Factor
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    ABSTRACT: γ-Aminobutyric acid B (GABAB) receptors and their ligands are postulated as potential therapeutic targets for the treatment of several brain disorders, including drug dependence. Over the past fifteen years positive allosteric modulators (PAMs) have emerged that enhance the effects of GABA at GABAB receptors and which may have therapeutic effects similar to those of agonists but with superior side-effect profiles. This review summarizes current preclinical evidence supporting a role of GABAB receptor PAMs in drug addiction in several paradigms with relevance to reward processes and drug abuse liability. Extensive behavioral research in recent years has indicated that PAMs of GABAB receptors may have a therapeutic efficacy in cocaine, nicotine, amphetamine and alcohol dependence. The magnitude of the effects observed are similar to that of the clinically approved drug baclofen, an agonist at GABAB receptors. Moreover, given that anxiolytic effects are also reported with such ligands they may also benefit in mitigating the withdrawal from drugs of abuse. In summary, a wealth of data now supports the benefits of GABAB receptor PAMs and clinical validation is now warranted.
    Neuropharmacology 06/2014; · 4.11 Impact Factor
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    ABSTRACT: The primary aim of the present study was to assess the possible associations between dopaminergic, serotonergic, and glutamatergic system-related genes and adverse events after antipsychotic treatment in paranoid schizophrenia patients. The second aim of the study was to compare the intensity of these symptoms between atypical (ziprasidone and olanzapine) and typical (perazine) antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT, MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of side effects (changes in body weights and extrapyramidal symptoms (EPS)) was measured at baseline and after 12 weeks of antipsychotic treatment. After 3 months of therapy, the weight increase was the greatest in the group treated with olanzapine and the least in the group treated with ziprasidone. None of the examined gene polymorphisms was associated with the body weight changes. Perazine treatment was associated with the significantly highest intensity of EPS. None of the examined polymorphisms was associated with the changes in extrapyramidal adverse events after antipsychotic treatment. The selected polymorphisms are not primarily involved in changes in body weights and EPS related to antipsychotic treatment in paranoid schizophrenia patients.
    Psychiatry research. 06/2014;
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    ABSTRACT: In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design to obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5 HT6/7/2A and D2 receptors, without interacting with M1 receptors and hERG channels. In vitro studies confirmed their antagonism of 5 HT7/2A and D2 receptors and weak interactions with key antitargets (M1R and hERG) associated with side effects. Marked 5 HT6 receptor affinities were also observed, notably for 6-fluoro-3-(piperidin-4-yl)-1,2-benzoxazole derivatives connected by a 3-4 unit alkyl linker with mono- or bi-cyclic, lipophilic arylsulfonamide moieties. N-[4-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]benzothiophene-2-sulfonamide (72) was characterized in vitro on 14 targets and anti-targets. It displayed dual blockade of 5 HT6 and D2 receptors and negligible interactions at hERG and M1 receptors. Unlike reference antipsychotics, 72 displayed marked antipsychotic and antidepressant activity in rats after oral administration, in the absence of cognitive or motor impairment. This profile is particularly attractive when targeting a fragile, elderly BPSD patient population.
    Journal of Medicinal Chemistry 05/2014; · 5.61 Impact Factor
  • The Journal of neuropsychiatry and clinical neurosciences 04/2014; 26(2):E21. · 2.34 Impact Factor
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    ABSTRACT: Objectives Increased consumption of carbohydrates and craving for sweets are considered core features of winter depression. Unfortunately, little is known about neural and behavioral correlates of these symptoms. The primary aim of the present study was to evaluate taste responses to sucrose solutions in depressed patients with seasonal affective disorder (SAD). Methods Intensity and pleasantness ratings of sucrose solutions, electrogustometric thresholds, and taste identification abilities were assessed in depressed patients with SAD and non-seasonal affective disorder (non-SAD), and in non-depressed controls. Results Electrogustometric thresholds and identification abilities did not differ between the study groups. There were no differences between the groups in intensity or pleasantness ratings of sucrose solutions (1-30%). The proportion of 'sweet likers', i.e. subjects rating the highest sucrose concentration as most pleasant, was similar in the controls, SAD, and non-SAD patients. Discussion The present results suggest that: (i) winter depression is not associated with major alterations in gustatory function; and (ii) sweet craving and increased consumption of carbohydrates in patients with winter depression is not secondary to altered responses to sweet tastants. More studies are needed to characterize hedonic responses of patients with SAD to other sweet and non-sweet foods.
    Nutritional Neuroscience 03/2014; · 1.65 Impact Factor
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    ABSTRACT: Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD.
    Archiv für Experimentelle Pathologie und Pharmakologie 03/2014; · 2.15 Impact Factor
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    ABSTRACT: Alcohol dependence is a common severe psychiatric disorder with a multifactorial etiology. Since the completion of the human genome project and with the increased availability of high-throughput genotyping, multiple genetic risk factors for substance-related disorders, including alcohol dependence, have been identified, but not all results could be replicated.
    Neuropsychobiology 01/2014; 70(2):77-94. · 2.37 Impact Factor
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    ABSTRACT: Anxiety, depression, and alcohol use disorders often go together. The aim of the present study was to evaluate anxiety- and depressive-like traits in selectively bred Warsaw alcohol high-preferring (WHP) and Warsaw alcohol low-preferring (WLP) rats. Alcohol-naïve WHP rats were more active in the open field test as compared to alcohol-naïve WLP rats. WHP rats made more central entries and spent more time in the central sector of the open field, i.e. presented less "neophobia", as compared to WLP subjects. The latter difference remained significant after controlling for the difference in locomotor activity as the anti-thigmotaxis ratio was also higher in WHP subjects. WHPs presented less freezing (i.e. less conditioned fear) than WLPs in the fear conditioning test. The difference in conditioned fear could not be explained by different pain sensitivity as the lines did not differ in pain threshold assessed in the flinch-jump test. WHPs were slightly less immobile in the Porsolt forced swim test as compared to WLPs. In conclusion, the present results suggest that alcohol high-preferring WHP rats show less anxiety- and depressive-like behavior than their low-preferring WLP counterparts.
    Pharmacology Biochemistry and Behavior 01/2014; · 2.82 Impact Factor
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    ABSTRACT: The aim of the study was to determine the influence of DRD2 gene polymorphisms in exon 8 G/A (rs 6276) in the promoter region -141 C Ins/Del (rs1799732) and the influence of ANKK-1 gene Taq-1A polymorphism (rs 1800497) on the preference of increasing sucrose concentrations in men with alcohol dependence. 63 male patients with alcohol dependence were genotyped for the above polymorphisms. Their preference for increasing sucrose concentrations was tested and their taste intensity perception of sucrose solutions was assessed. The patients were tested with the 'Sniffin' Sticks' olfactory test. We found a statistically significant association between some alleles of ANKK 1 gene Taq 1A polymorphisms and sucrose preference in the subjects. The A1 Taq 1A allele determined hedonistic response to the two highest concentrations of sucrose. No association was found regarding the other two polymorphisms (in the promoter region and in the exon 8 of the DRD2 gene). Study results suggest Taq-1A polymorphism plays a role in the preference to high concentrations of sucrose and its potential association with alcohol dependence pathogenesis.
    Psychiatria Danubina 12/2013; 25(4):371-8. · 0.63 Impact Factor
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    ABSTRACT: Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with motor and cardiac side-effects which are problematic in elderly patients. A need therefore exists for drugs that are better suited for treatment of BPSD. we used in vitro cellular and in vivo behavioural tests to characterize ADN-1184, a novel arylsulfonamide ligand with potential utility for treatment of BPSD. ADN-1184 exhibits substantial 5-HT6 /5-HT7 /5-HT2A /D2 receptor affinity and antagonist properties in vitro. In tests of antipsychotic-like activity, it reversed MK-801-induced hyperactivity and stereotypies, and inhibited Conditioned Avoidance Response (CAR) (MED = 3 mg/kg i.p.). Remarkably, ADN-1184 also reduced immobility time in the forced swim test at low doses (0.3 and 1 mg/kg i.p.; higher doses were not significantly active). Notably, up to 30 mg/kg ADN-1184 did not impair memory performance in the passive avoidance test or elicit significant catalepsy and only modestly inhibited spontaneous locomotor activity (MED = 30 mg/kg i.p.). ADN-1184 combines antipsychotic-like with antidepressant-like properties without interfering with memory function or locomotion. This profile is superior to that of commonly-used atypical antipsychotics tested under the same conditions (Kołaczkowski et al., submitted) and suggests that it is feasible to identify drugs that improve behavioural and psychological symptoms without exacerbating cognitive deficit or movement impairment which are of particular concern in dementia patients.
    British Journal of Pharmacology 11/2013; · 5.07 Impact Factor
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    ABSTRACT: Zolpidem is a non-benzodiazepine hypnotic drug acting preferentially at α1-containing GABAA receptors expressed in various parts of the brain, including the basal ganglia. The aim of the present study was to provide preliminary characteristics of zolpidem-induced catalepsy in Wistar rats. Zolpidem (2.5-10.0mg/kg), but not diazepam and midazolam, produced dose-dependent cataleptic responses in the bar test, which were similar to those produced by a reference antipsychotic drug, haloperidol. Zolpidem-induced catalepsy was abolished by a benzodiazepine site antagonist, flumazenil (5.0mg/kg), D2/3 receptor agonist, quinpirole (1.0mg/kg), and a non-competitive NMDA receptor antagonist, MK-801 (0.1mg/kg), but not by a non-selective opioid receptor antagonist, naltrexone (3.0mg/kg). The present results indicate that systemic injections of zolpidem may produce short-lasting, neuroleptic-like catalepsy in the rat.
    Neuroscience Letters 10/2013; · 2.03 Impact Factor
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    ABSTRACT: It is known that extract from root of Salvia miltiorrhiza (SM) is involved in reducing alcohol intake in animal models. Since ethanol can act preferentially via selected brain GABAA receptor subtypes, therefore the aim of this study was to assess an influence of SM on mRNA expression of GABAA receptor subunits (a1-4, d, gL, gS) genes in brain of ethanol drinking rats after chronic exposure. The studies were performed on male Warsaw high-alcohol-preferring (WHP) and Warsaw lowalcohol-preferring (WLP) Wistar rats. The rats were treated with the hydroalcoholic (1:1) extract from root of SM (150 mg/kg, p.o.) or 5.0% Tween 80 (vehicle) for 28 consecutive days and mRNA expression of the GABAA receptor subunits genes in cortex, striatum and hippocampus were measured by RT-PCR analysis using Master SYBR Green with GAPDH as a housekeeping gene for normalization. SM significantly lowered alcohol intake (23 %) only in WHP animals. WHP vehicle-treated rats showed a decrease of mRNA expression of d subunit in cortex and a4 subunit in striatum, whereas an increase of a3 and gS subunits in hippocampus was found when compared with WLP rats. SM administration affected the mRNA expression in WHP rats by lowering their hippocampal a2, a3 and gS subunits and simultaneously enhancing of a1, a4, gL and gS subunits. In WLP animals the lowering of a4 mRNA expression in striatum was observed only. In conclusion, the results have shown that SM effect on drinking behavior in rats can be coupled with a modulation of GABAA receptor subtypes expression in several brain regions. This work was supported by Polish National Science Centre grant N405678040.
    15th European Behavioural Pharmacological Society (EBPS) Biennial Meeting, Espace Encan, La Rochelle, France; 09/2013
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    ABSTRACT: INTRODUCTION AND HYPOTHESIS: The aim of the present study was to determine possible correlations between mesh retraction after anterior vaginal mesh repair and de novo stress urinary incontinence (SUI), overactive bladder (OAB), and vaginal pain symptoms. METHODS: One hundred and three women with symptomatic prolapse of the anterior vaginal wall, stages 3 and 4 based on the Pelvic Organ Prolapse Quantification (POP-Q) system, underwent Prolift anterior™ implantation. At a 6-month follow-up, the patients were interviewed for de novo SUI, OAB, and vaginal pain, and underwent an introital/transvaginal ultrasound examination to measure the mesh length in the midsagittal plane. RESULTS: Mesh retraction was significantly larger in a subgroup of patients (n = 20; 19.4 %) presenting de novo OAB symptoms on the follow-up assessment compared with those without this complication (5.0 cm vs. 4.3 cm; p < 0.05). Mesh retraction was also significantly larger in a subgroup of patients (n = 23; 22.3 %) reporting postoperative vaginal pain compared with the women who did not report any postoperative vaginal pain (5.3 cm vs. 4.2 cm; p < 0.01). A significant correlation was found between mesh retraction and the severity of vaginal pain (R = 0.4, p < 0.01). Mesh retraction did not differ between patients with de novo SUI symptoms and those without this complication. CONCLUSIONS: Mesh retraction assessed on ultrasound examination after anterior vaginal mesh repair may correlate with de novo OAB symptoms and vaginal pain.
    International Urogynecology Journal 06/2013; · 2.17 Impact Factor
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    ABSTRACT: Pleasant tastes and odors are considered phylogenetically old natural rewards and their hedonic evaluation is regarded as a good indicator of the reward system function. The primary aim of the present study was to compare pleasantness ratings of sucrose solutions (1-30%, w/w) and sweet liking/disliking status in 20 patients with Parkinson's disease (PD) and in 20 age-matched healthy controls. In addition, basic sensory aspects of gustatory (intensity ratings, electrogustometric thresholds) and olfactory function (identification abilities in the Sniffin' Stick test) were assessed in both groups. The number of odors rated as pleasant, unpleasant, and neutral was also compared. As expected, the PD patients showed a significant impairment in olfactory identification abilities. There were no differences between the PD patients and controls in electrogustometric thresholds. Rated intensity of higher sucrose concentrations did not differ between the groups. The PD patients tended to rate water taste as more intense in comparison with the controls. Pleasantness ratings of sucrose solutions, the proportion of subjects rating 30% sucrose as the most pleasant (sweet likers), and the number of odors rated as pleasant did not differ between the study groups. The present results suggest that PD does not lead to any obvious alterations in pleasantness ratings of chemosensory stimuli. The study requires replication in larger samples.
    Journal of the neurological sciences 04/2013; · 2.32 Impact Factor
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    ABSTRACT: Introduction. Schizophrenic patients present cognitive dysfunctions which are regarded to be one of endophenotypical markers predisposing to schizophrenia. Currently, schizophrenia can be treated as a neurodegenerative and neurodeveloping disease with genetic background. Objective. Assessment of the possible positive effect of neuropsychological rehabilitation in schizophrenia, in patients presenting cognitive dysfunctions. An additional aim was to verify the hypothesis that some genetic polymorphisms can be a prognostic factor for success in neuropsychological rehabilitation. Material and methods. 41 participants and 40 control subjects were randomly selected. Both groups had the diagnosis of paranoid schizophrenia. Cognitive functions were checked with the Wisconsin Card Sorting Test, Trail Making Test, and Stroop Test at the beginning and end of the experiment. In the research group, each patient trained with the rehabilitation programme RehaCom, whereas the control group did not receive such training. Genes COMT rs4680 and BDNF rs6265 were analysed in the genetic part of study. Results. RehaCom procedures appear to be useful in the neuropsychological rehabilitation of cognitive dysfunctions in patients diagnosed with schizophrenia. The research group showed a moderate improvement in the training programmes. Analysis of parameters obtained in the neuropsychological tests showed a slight improvement in both groups. At the present time, analysis of the polymorphisms of genes cannot be treated as a prognostic factor for the success of neuropsychological rehabilitation because statistical analyses showed few dependences with little statistical significance. Conclusions. Cognitive rehabilitation produces moderate improvement in cognitive functioning.
    Annals of agricultural and environmental medicine: AAEM 03/2013; 20(1):77-81. · 3.06 Impact Factor
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    ABSTRACT: Ninety-eight cigarette smokers with ischemic stroke were recruited between December 2006 and December 2008 in an urban hospital. Smoking status and reasons for quit attempts after stroke were assessed at 3-month follow-up. 73% of patients (72/98) made at least one quit attempt between stroke onset and the follow-up visit. 47% of quit attempters (34/72) declared that stroke was the major reason for quitting. The patients reporting stroke as the major reason for quitting were more likely to be abstinent at the follow-up as compared to the patients who did not (61.8 vs. 36.8%). The study suggests that some motives for quitting smoking are associated with a higher chance for short-term abstinence in stroke patients.
    European Addiction Research 07/2012; 18:275-8. · 2.36 Impact Factor
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    ABSTRACT: An assessment of the acoustic startle response (ASR) and prepulse inhibition (PPI) of ASR in laboratory animals is used to model human anxiety and psychotic states, respectively. The aim of the study was to evaluate ASR and PPI in alcohol-naive male and female Warsaw alcohol high-preferring (WHP) and Warsaw alcohol low-preferring (WLP) rats. ASR and PPI were assessed in two separate experiments by using the SR-LAB apparatus (San Diego Instruments, San Diego, CA, USA). In the ASR session, animals (n = 13-16 rats per group) were exposed to startling stimuli of different intensities (72, 84, 98, 112 and 124 dB) in a random order. In the PPI session, prepulse stimuli (78, 81, 84 and 90 dB) preceded a pulse startling stimulus (120 dB) in a random order. The background white noise was set at 70 dB. PPI was calculated according to the formula: [(startle amplitude in pulse alone trials-startle amplitude in prepulse-and-pulse trials)/startle amplitude in pulse alone trials] 100%. The WHP males exhibited higher startle amplitudes in response to 112 dB stimuli when compared with their WLP counterparts. The WHP females showed higher startle reactivity to 112 and 124 dB stimuli when compared with the WLP females. There were no differences between the WHPs and WLPs in PPI of ASR. The results of the present study suggest that exaggerated startle responses can be a physiological/behavioral marker of a propensity to abuse alcohol.
    Alcohol and Alcoholism 04/2012; 47(4):386-9. · 1.96 Impact Factor
  • The Journal of neuropsychiatry and clinical neurosciences 03/2012; 24(2):E32. · 2.34 Impact Factor
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    ABSTRACT: Individuals prone to drug self-administration may be vulnerable not only to a single drug reinforcer but to a variety of drug reinforcers. It has been shown that two thirds of alcoholics regularly use drugs other than ethanol (alcohol). Up to 30% of alcohol-dependent patients report concurrent misuse of cocaine. The aim of the present study was to investigate intravenous cocaine self-administration in selectively bred, alcohol-preferring WHP (Warsaw high-preferring) and non-preferring WLP (Warsaw low-preferring) rats. It was hypothesized that WHPs could be more prone to cocaine self-administration in comparison to WLPs. Rats from both lines were allowed to nose-poke for cocaine infusions (0.33 mg/kg/infusion) under the FR-1, FR-2, and FR-3 schedule of reinforcement. Dose-response curves were assessed with increasing doses of cocaine (0.03, 0.1, 0.33, 1.0mg/kg/infusion). The WHP and WLP rats did not differ in cocaine self-administration. Both groups quickly acquired nose-poke responding for cocaine, presented a similar response profile when the schedule of reinforcement was increased from FR-1 to FR-3, and similar sensitivity to cocaine in the dose-response test. The present results may indicate that the selective breeding of alcohol-preferring WHP and alcohol non-preferring WLP rats did not lead to differences in cocaine's rewarding effects as assessed in the self-administration procedure.
    European journal of pharmacology 11/2011; 674(2-3):275-9. · 2.59 Impact Factor

Publication Stats

964 Citations
260.79 Total Impact Points


  • 1995–2014
    • Institute of Psychiatry and Neurology
      Warszawa, Masovian Voivodeship, Poland
  • 2011
    • Nencki Institute of Experimental Biology
      Warszawa, Masovian Voivodeship, Poland
  • 2000–2010
    • Medical University of Warsaw
      • Katedra i Klinika Otolaryngologiczna
      Warsaw, Masovian Voivodeship, Poland
  • 2009
    • Medical University of Gdansk
      Danzig, Pomeranian Voivodeship, Poland
  • 2006–2008
    • Pomeranian Medical University in Szczecin
      • Department of Public Health
      Stettin, West Pomeranian Voivodeship, Poland
  • 2003
    • Polish Academy of Sciences
      • Department of Pharmacology
      Warsaw, Masovian Voivodeship, Poland