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1
Artykuł dostępny w postaci pełnego tekstu - kliknij by otworzyć plik
Content available

Nowe uzależnienia XXI wieku

100%
Filip M.
Wszechświat
|
2013
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tom 114
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nr 04-06
2

Therapeutic potential of 5-HT2C receptor ligands towards cocaine addiction

63%
Filip M., Zaniewska M.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr S
Serotonin (5-HT) neurotransmission controls the brain physiology and contributes to the etiology of many neuropsychiatric disorders. One of the key modulators of 5-HT system is the 5-HT2C receptor which regulates feeding, satiety, mood and cognition as well as underlines the mechanisms of depression, schizophrenia and addiction (Filip and Bader 2009). Among abused drugs, cocaine addiction creates serious health and legal implications in developed world while no medication is approved for the treatment of cocaine addiction. Detailed preclinical pharmacological analyses with several selective 5-HT2C receptor ligands have provided consistent proofs that these receptors contribute to cocaine acute and repeated behaviors. In general, systemic pretreatment of 5-HT2C receptor agonists attenuates, while antagonists enhance cocaine-induced psychomotor activation, reward and reinforcement as well as subjective (discriminative stimulus) effects in laboratory animals (Filip et al. 2010). 5-HT2C receptors are also important neural mediators in the circuitry underlying cocaine-seeking and -taking behaviors since their stimulation attenuated conditioned hyperactivity to cocaine and the priming effect of acute cocaine, cue- or stresscontrolled cocaine-seeking. More importantly, the inhibitory action of 5-HT2C receptor agonists on the reinstatement of cocaine seeking, when extrapolated to abstinent human addicts, suggest therapeutic potential for these drugs as pro-abstinence and anti-relapse ones. The main shortcoming of 5-HT2C receptor agonists for cocaine addiction may be their inhibitory effects in motivated behaviors (including food consumption) as found in preclinical research (Neisewander and Acosta 2007) and recent clinical trials (Smith et al. 2009). This study was supported by the statutory activity of the Institute of Pharmacology Polish Academy of Sciences (Krakow)
3

Impact of serotonin (5-HT) receptor stimulation on the locomotor and discriminative effect of amphetamine and cocaine in rats

63%
Filip M., Przegalinski E.
Acta Neurobiologiae Experimentalis
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1997
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tom 57
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nr 5
4

The role of corticosterone in behavioral sensitization to cocaine in rats

51%
Filip M., Siwanowicz J., Nowak E., Przegalinski E.
Acta Neurobiologiae Experimentalis
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1999
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tom 59
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nr 3
5

An impact of enhanced endocannabinoid/endovanilloid neurotransmission on the behavioral effects of cocaine in rats

51%
Filip M., Adamczyk P., Bystrowska B., Przegalinski E.
Acta Neurobiologiae Experimentalis
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2011
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tom 71
|
nr S
The endocannabinoid system consists of cannabinoid (CB) receptors CB1 and CB2, several endogenous ligands (e.g., anandamide and 2-arachidonoylglycerol ; 2-AG), and many membrane-bound metabolizing enzymes. Endocannabinoids and mainly CB1 receptors are important for regulation of goal-maintained behaviors as well as for different pathologies affecting these processes. CB1 receptors modulate function on dopamine transmission through indirect mechanisms involving GABA or glutamate neurons while anandamide and certain eicosanoid-derived cannabinoids may also directly activate transient receptor potential vanilloid-1 (TRPV1) channels found in some dopaminergic pathways, thus allowing a direct regulation of dopamine function. Recent, preclinical reports indicate, that drugs affected endocannabinoid/endovanilloid system may play key role in drug addiction, especially in reinstatement of cocaine seeking behavior (Filip et al. 2006). Latest results coming from our laboratories indicate a role for CB1, CB2 or TRPV1 receptors to control food self-administration but not cocaine rewarding actions. We also report inhibitory effects of CB1, CB2 or TRPV1 receptor antagonists on drug-primed cocaine-seeking behavior. Only CB1 receptor antagonism attenuated cue-induced reinstatement of cocaine seeking. Ex vivo autoradiography (CB1 receptor binding measurements) and the LC/MS system (endocannabinoid/endovanilloid levels) revealed that chronic cocaine (either active or passive administration) evokes upregulation of rat brain CB1 receptors lasting until 10 days of cocaine withdrawal while self-administered cocaine (but not given passively in a “yoked” procedure) modulates the brain levels of anandamide and 2-AG. This study was supported by the grants by the Ministry of Science and Higher Education (Poland) to P.A. and B.B., as well as by the statutory activity of the Institute of Pharmacology Polish Academy.
6
Content available remote

Maternal high-fat diet during pregnancy and lactation provokes depressive-like behavior and influences the irisin/brain-derived neurotrophic factor axis and inflammatory factors in male and female offspring in rats

51%
Gawlinska K., Gawlinski D., Przegalinski E., Filip M.
Journal of Physiology and Pharmacology
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2019
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tom 70
|
nr 3
7

The use of unbiased conditioned place preference procedure as the predictive analysis of vulnerability to psychostimulant addiction in rats

51%
Niedzielska E., Pomierny-Chamiolo L., Filip M.
Acta Neurobiologiae Experimentalis
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2014
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tom 74
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nr 3
As in humans, also in laboratory animals, addiction phenotype including drug craving and relapses, develops only in about 20% subjects following initial drug abuse. The aim of our study was to verify if the conditioned place preference (CPP) paradigm can serve as a model for determination of the variable vulnerability to drug addiction. We used male Wistar rats (250–300 g) housed under standard laboratory conditions. Animals were exposed to either vehicle (n=20) or to the psychostimulant cocaine (15 mg/kg, ip; n=64) during 10 days with CPP. As a result, 15 animals (i.e., 23.4% of all experimental animals) that performed unbiased version of CPP, spent more time in cocaine-paired chamber in test in comparison to pretest (P<0.0005 vs. control); those rats were classified as addiction vulnerable. In conclusion, our results suggest that unbiased conditioned place preference procedure can serve as an animal model for predictive analysis of vulnerability to psychostimulant addiction in rats. Moreover, it also gives the opportunity to study the phenotype of animals (so called addiction-resistant) which did not develop drugassociated environment-linked craving.
8

An endogenous neuroprotective compound-lMeTTQ-prevents the cocaine addiction in self-administration model in rat:neurochemical correlates

51%
Antkiewicz-Michaluk L., Romanska R., Filip M., Michaluk J.
Acta Neurobiologiae Experimentalis
|
2005
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tom 65
|
nr 3
9

Maternal high fat diet provokes depressive-like behavior in offspring rats and vulnerability to cocaine addiction

51%
Gawlinski D., Frankowska M., Kluska K., Filip M.
Acta Neurobiologiae Experimentalis
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2017
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tom 77
|
nr Suppl.1
INTRODUCTION: The epidemiological and animal studies underline that composition of maternal diet (e.g., high fat diet, HFD) is associated with an increased susceptibility to several health problems in the adult offspring, including risk of a cluster of behavioral disorders such as depression. AIM(S): The aim of this study was to investigate the effect of maternal HFD on the offspring phenotype assessed in locomotor activity study, forced swim test (FST) and cocaine self-administration. METHOD(S): Wistar rat dams were maintained ad libitum either on a special HFD (35% crude fat) or standard rodent chow during gestation and lactation (21 days). At postnatal day (PND) 27, the male and female litters were separated from their mother and were switched to a standard diet. Locomotor activity was recorded for 120 min at PND 28 and 63. At PND 34 the FST was performed. Moreover, at PND 63 male rats were introduced into two different cocaine self-administration protocols: 1) stable cocaine dose (0.5 mg/kg/inf.) with increasing schedule of reinforcement fixed ratio (FR) 1 to 5 or 2) increasing cocaine doses (0.25–1 mg/kg/inf.) and stable FR1. Following 10 extinction days, male rats were tested for the response reinstatement of drug-seeking behavior induced by cocaine-priming dose (10 mg/kg, i.p.) and cue (tone+light). RESULTS: HFD group exhibited depressive-like phenotype, characterized by increased immobility time and decreased climbing in both tested time points what was not affected by the changes in basal locomotor activity. The HFD rats displayed an attenuation of the cocaine-associated lever presses and cocaine intake during the acquisition/maintenance of cocaine self-administration and lower response to relapse behavior evoked by cocaine priming or the drug-associated conditioned stimulus. CONCLUSIONS: Our data suggest the influence of maternal HFD on the offspring’s behavior, however underlying molecular mechanism requires further investigations. FINANCIAL SUPPORT: Supported by research grant UMO-2016/21/B/N24/00203 from the NCN (Poland).
10
Content available remote

Brain region-dependent changes in the expression of endocannabinoid-metabolizing enzymes in rats following antidepressant drugs

51%
Smaga I., Gawlinski D., Brodowicz J., Filip M.
Journal of Physiology and Pharmacology
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2019
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tom 70
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nr 5
11

Bi-directional interaction between nicotine and serotonin (5-HT)2C receptors - behavioural and molecular aspects

51%
Zaniewska M., Filip M., Bader M.
Acta Neurobiologiae Experimentalis
|
2011
|
tom 71
|
nr S
Recent data point to a role of serotonin (5-HT) and its receptors, mainly 5-HT2C receptor subtype, in the effects of nicotine - the key addictive component in cigarettes. Our series of studies performed on rats showed that pharmacological blockade of 5-HT2C receptors augmented the locomotor responses to acute nicotine, while activation of these receptors diminished nicotine-induced hyperactivity, the expression of behavioural sensitisation and conditioned locomotor activity as well as depression-like behaviour evoked by nicotine withdrawal. Our more recent studies demonstrated that nicotine challenge to nicotine-sensitised rats decreased [3H]mesulergine binding to 5-HT2C receptors in the prefrontal cortex, while nicotine withdrawal reduced receptor labelling in the ventral dentate gyrus and thalamic nuclei. To identify the mechanism associated with changes in radioligand binding, we analysed the pattern of 5-HT2C receptor mRNA editing (a posttranscriptional modification that may result in functionally different receptor isoforms) following repeated nicotine administration. Interestingly, our preliminary deep sequencing data showed significant decreases in 5-HT2C receptor mRNA editing in the hippocampus of nicotine-withdrawn animals. Such an alteration in editing may affect the availability of binding sites for 5-HT2C receptor radioligand and could partially explain changes in radioligand binding noted in this brain region. Taken together, our data support the existence of bi-directional interaction between 5-HT2C receptors and nicotine. Clear effects of 5-HT2C receptor agonists to ameliorate symptoms associated with nicotine dependence have been shown. On the other hand, the ability of nicotine to affect 5-HT2C receptor binding and editing has also been reported. Present data show a new direction in the search for efficient anti-nicotinic drugs and the possibility of using 5-HT2C receptor agonists as adjuncts to smoking cessation therapy.
12

GABA(B) receptor ligands as a pharmacotherapy for cocaine addiction-preclinical studies

51%
Filip M., Frankowska M., Przegalinski E.
Acta Neurobiologiae Experimentalis
|
2007
|
tom 67
|
nr 3
13

Effects of direct and indirect dopamine receptor agonists on the cannabinoid CB1 receptor agonist CP 55,940-induced discrimination

51%
Frankowska M., Filip M., Przegalinski E.
Acta Neurobiologiae Experimentalis
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2005
|
tom 65
|
nr 3
14

Role of 5-HT reuptake inhibition and 5-HT1A receptors in the discriminative stimulus effects of fenfluramine

51%
Filip M., McCreary A. C., Cunningham K. A.
Acta Neurobiologiae Experimentalis
|
1999
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tom 59
|
nr 3
15
Artykuł dostępny w postaci pełnego tekstu - kliknij by otworzyć plik
Content available

Role of 5-hydroxytryptamine 1B receptors and 5-hydroxytryptamine uptake inhibition in the cocaine-evoked discriminative stimulus effects in rats

51%
Filip M., Nowak E., Papla I., Przegalinski E.
Journal of Physiology and Pharmacology
|
2001
|
tom 52
|
nr 2
16
Artykuł dostępny w postaci pełnego tekstu - kliknij by otworzyć plik
Content available

Effect of adrenalectomy and corticosterone on cocaine-induced sensitization in rats

51%
Przegalinski E., Filip M., Siwanowicz J., Nowak E.
Journal of Physiology and Pharmacology
|
2000
|
tom 51
|
nr 2
17
Artykuł dostępny w postaci pełnego tekstu - kliknij by otworzyć plik
Content available

On the role of serotonin2A-2C receptors in the sensitization to cocaine

51%
Filip M., Nowak E., Papla I.
Journal of Physiology and Pharmacology
|
2001
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tom 52
|
nr 3
18
Content available remote

Effects of 5-HT1B receptor ligands microinjected into the accumbal shell or core on the cocaine-induced locomotor hyperactivity in rats

51%
Przegalinski E., Filip M., Papla I., Czepiel K.
Journal of Physiology and Pharmacology
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2002
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tom 53
|
nr 3
The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 µg/side) or CP 93129 (0.1-10 µg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 µg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 µg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 µg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 µg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.
19

Zaburzenia funkcji śródbłonka naczyń wywołane stresem oksydacyjnym i stanem zapalnym w okołonaczyniowej tkance tłuszczowej

45%
Filip M., Maciag J., Nosalski R., Korbut R., Guzik T.
Postępy Biochemii
|
2012
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tom 58
|
nr 2
20

Changes of Galpha(q), Galpha(11) and Galpha(12) mRNA expression levels in rat prefrontal cortex and amygdala after reinstatement of cocaine-seeking behavior

45%
Zelek-Molik A., Kreiner G., Filip M., Wydra K., Nalepa I.
Acta Neurobiologiae Experimentalis
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2011
|
tom 71
|
nr S
Inhibition of monoamine transporters by a psychostimulant, cocaine, increases the monoamines availability at synaptic cleft and leads to the enhanced stimulation of monoaminergic postsynaptic receptors. G proteins represent the down-stream connectors from receptors to intracellular signalling. The aim of the study was to assess the expression of Gα(q), Gα(11) and Gα(12) mRNAs following reinstatement of cocaine-seeking behaviour in the prefrontal cortex (PFC) and the amygdala (AMY) of male Wistar rats using a “yoked” procedure and RT-PCR technique. We found that phases of cocaine-seeking behavior differently influenced the Gα subunits depending on the brain structure analyzed. Cocaine self-administered for 18 days induced a significant increase of mRNA levels of all Gα subunits (by ~23% for Gα12 and Gα11, and by 46% for Gαq vs yoked) in the PFC. After 10 days withdrawal from cocaine when no change in G proteins was observed, reinstatement induced by priming dose of the drug decreased G12 and Gq. The effect was more pronounced after combination of the cocaine with cue previously associated with cocaine self-administration and was noticed in G11 as well. In AMY, changes in the expression of Gα mRNAs induced by cocaine self-administration dependent on environmental cues paired with cocaine. Cocaine self-administration decreased (by ~24%) all G protein mRNAs while opposite effect was observed when cocaine self-administration was paired with cue stimulus. Withdrawal from cocaine induced 2-fold increase in mRNA level of three G proteins. On the contrary, the reinstatement induced by the cue decreased significantly Gα mRNAs to the same degree as did its combination with cocaine-priming. Our study provides the first evidence that alterations of G proteins mRNA expression can be conditioned by environmental stimuli paired with cocaine administration. Supported by statutory funds of the Institute of Pharmacology PAS.
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