Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the drugs.
- Klíčová slova
- Anxiety-related behavior, Elevated plus-maze test, Prenatal methamphetamine, Sensitization, Sex-dimorphism,
- MeSH
- analgetika farmakologie MeSH
- analýza rozptylu MeSH
- bludiště - učení účinky léků MeSH
- časové faktory MeSH
- estrální cyklus účinky léků MeSH
- krysa rodu Rattus MeSH
- methamfetamin toxicita MeSH
- N-methyl-3,4-methylendioxyamfetamin farmakologie MeSH
- pátrací chování účinky léků MeSH
- serotoninové látky farmakologie MeSH
- sexuální faktory MeSH
- stimulanty centrálního nervového systému toxicita MeSH
- těhotenství MeSH
- úzkost chemicky indukované MeSH
- zpožděný efekt prenatální expozice chemicky indukované patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- analgetika MeSH
- methamfetamin MeSH
- N-methyl-3,4-methylendioxyamfetamin MeSH
- serotoninové látky MeSH
- stimulanty centrálního nervového systému MeSH
The present study was designed to investigate the acute relaxing effect of phytoestrogen resveratrol on isolated porcine coronary arteries and to determine the mechanisms underlying its vasodilatation. Rings of porcine coronary arteries were suspended in organ baths containing Krebs-Henseleit solution, and then isometric tension was measured. Resveratrol concentration-dependently relaxed arterial rings precontracted with 30 mM KCl. The IC(50) value of resveratrol was 38.67+/-3.21 microM. Incubation with N(omega)-L-nitro-arginine (L-NNA), endothelium removal or the presence of a potent inhibitor of protein tyrosine phosphatase sodium orthovanadate partly decreased the relaxation induced by resveratrol. However, the relaxation induced by resveratrol was unaffected by the estrogen receptor antagonist tamoxifen, the inhibitor of prostanoid synthesis indomethacin, the antagonist of beta-adrenoceptors propranolol or the protein synthesis inhibitor, cycloheximide. In addition, resveratrol significantly decreased the contractile responses of 5-HT, KCl and CaCl(2), and shifted their cumulative concentration-response curves to the right. These results suggest that the mechanisms of vasorelaxation induced by resveratrol are heterogeneous, two mechanisms participating partially in the relaxation of porcine coronary artery were detected in the study, one being the nitric oxide released from the endothelium, the other causing inhibition of Ca(2+) influx, but estrogen receptors were not involved in resveratrol-induced relaxation.
- MeSH
- beta-adrenergní receptory metabolismus MeSH
- cévní endotel účinky léků MeSH
- chlorid draselný farmakologie MeSH
- inhibitory enzymů farmakologie MeSH
- koronární cévy účinky léků MeSH
- koronární cirkulace účinky léků MeSH
- nitroarginin farmakologie MeSH
- oxid dusnatý metabolismus MeSH
- prasata MeSH
- prostaglandiny metabolismus MeSH
- resveratrol MeSH
- serotonin farmakologie MeSH
- serotoninové látky farmakologie MeSH
- stilbeny farmakologie MeSH
- techniky in vitro MeSH
- vápník metabolismus MeSH
- vazodilatace účinky léků MeSH
- vazodilatancia farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-adrenergní receptory MeSH
- chlorid draselný MeSH
- inhibitory enzymů MeSH
- nitroarginin MeSH
- oxid dusnatý MeSH
- prostaglandiny MeSH
- resveratrol MeSH
- serotonin MeSH
- serotoninové látky MeSH
- stilbeny MeSH
- vápník MeSH
- vazodilatancia MeSH
5-Hydroxytryptamine (5-HT) can be released from mast cells and platelets through an IgE-dependent mechanism and may play a role in the pathogenesis of allergic bronchoconstriction. However, the effect of 5-HT on ion transport by the airway epithelium is still controversial. The objective of this study was to determine whether 5-hydroxytryptamine (5-HT) regulates NaCl transport by different mechanisms in the apical and basolateral membrane of tracheal epithelia. We studied the rat tracheal epithelium under short-circuit conditions in vitro. Short-circuit current (I(sc)) was measured in rat tracheal epithelial monolayers cultured on porous filters. 5-HT inhibited Na(+) absorption [measured via Na(+) short-circuit current (I(Na)(sc))] in the apical membrane and stimulated Cl(-) secretion [measured via Cl(-) short-circuit current (I(Cl)(sc))] in the basolateral membrane. Functional localization using selective 5-HT agonists and antagonists suggest that I(Cl)(sc)is stimulated by the basolateral membrane-resident 5-HT receptors, whereas I(Na)(sc) is inhibited by the apical membrane-resident 5-HT2 receptors. The basolateral addition of 5-HT increases intracellular cAMP content, but its apical addition does not. The addition of BAPTA/AM blocked the decrease of I(Na)(sc)which was induced by the apical addition of 5-HT, and 5-HT increased intracellular Ca concentrations. These results indicate that 5-HT differentially affects I(Na)(sc)and I(Cl)(sc)across rat tracheal monolayers through interactions with distinct receptors in the apical and the basolateral membrane. These effects may result in an increase of water movement towards the airway lumen.
- MeSH
- AMP cyklický metabolismus MeSH
- chlorid sodný farmakokinetika MeSH
- elektrofyziologie MeSH
- epitelové buňky cytologie účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- membránové potenciály účinky léků MeSH
- polarita buněk fyziologie MeSH
- potkani Sprague-Dawley MeSH
- receptory serotoninové fyziologie MeSH
- respirační sliznice cytologie MeSH
- serotonin farmakologie MeSH
- serotoninové látky farmakologie MeSH
- signální transdukce účinky léků MeSH
- trachea cytologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- AMP cyklický MeSH
- chlorid sodný MeSH
- receptory serotoninové MeSH
- serotonin MeSH
- serotoninové látky MeSH
Behavioral effects of +/-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are relatively well described in humans as well as in animals. However, little is known about gender differences to the effects of MDMA. The aim of our study was to evaluate gender differences in stimulant effects of MDMA (2.5, 5.0, and 10.0 mg/kg subcutaneously (s.c.)) in male and female Wistar rats. We have used three behavioral methods (activity cage, open field, and elevated plus-maze) each describing a different pattern of spontaneous behavior. In the activity cage, 30 min after the MDMA administration, horizontal and vertical locomotor activities were registered for a period of 3 min. In the open field test rats were placed into an arena 15 min after drug treatment and locomotor activity was registered for a period of 30 min. Finally, in the elevated plus-maze test, rats were given MDMA 30 min prior to measurements and subsequently they were tested in the maze for a period of 5 min. In our experiments we observed a dose-dependent locomotion-enhancing effect of MDMA both in male and female rats in both locomotor tests. Female rats were more sensitive to the locomotor-stimulating effect than males in both tests, suggesting higher sensitivity to the stimulatory effect of MDMA. Further on, MDMA increased thigmotaxis in female rats in the open field test and decreased "anxious-like" behavior in the elevated plus-maze in both genders. In conclusion, we observed higher sensitivity of females to the locomotor-stimulant effect of MDMA. Increased sensitivity of females to the behavioral effects of MDMA can be explained by increased reactivity of serotonergic and dopaminergic systems.
- MeSH
- bludiště - učení účinky léků MeSH
- chování zvířat účinky léků MeSH
- krysa rodu Rattus MeSH
- N-methyl-3,4-methylendioxyamfetamin farmakologie MeSH
- pátrací chování účinky léků MeSH
- pohlavní dimorfismus * MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- serotoninové látky farmakologie MeSH
- úzkost farmakoterapie prevence a kontrola MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- N-methyl-3,4-methylendioxyamfetamin MeSH
- serotoninové látky MeSH