There is accumulating evidence that methamphetamine (MA) is a widely abused drug popular among pregnant women. MA exposure is associated with changes in the function of neurotransmitter systems, namely the dopaminergic, serotonergic and glutamatergic systems. Since N-methyl-D-aspartate receptors (NMDA) are affected by MA-induced glutamate release, we assessed the expression of NMDAR subunits (NR1, NR2A, and NR2B) and postsynaptic density protein 95 (PSD-95), which is connected with NMDAR. We measured the expression of these proteins in adolescent (30 days old) and adult (60 days old) rat males exposed to MA during the entire prenatal period and compared them with the same parameters in age matched saline-exposed rats. There was a significant increase in the NR1 and NR2B subunits in the hippocampus of adult males, but not in adolescent males. We identified a significant change in adult MA-induced rats when compared to adult controls for NR2A and NR2B, while in adolescent MA rats this change was close to the boundary of significance. In summary, our study suggests that prenatal MA exposure is connected with changes in NMDAR subunit expression in adult rats but not in adolescent rats.
- MeSH
- hipokampus účinky léků metabolismus MeSH
- methamfetamin toxicita MeSH
- novorozená zvířata MeSH
- podjednotky proteinů metabolismus MeSH
- potkani Sprague-Dawley MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- signální transdukce účinky léků MeSH
- stárnutí MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- methamfetamin MeSH
- podjednotky proteinů MeSH
- receptory N-methyl-D-aspartátu MeSH
The aim of the present study was to compare the response to sub-chronic application of methamphetamine (MA) in adulthood in male and female rats prenatally exposed to the same drug. The spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to 5 mg/kg MA or saline (SAL) were tested in a Laboras apparatus (Metris B.V., Netherlands) for five consecutive days, 1 hr daily. MA 1 mg/kg or SAL were used as a challenge prior to testing. Our results showed that rats prenatally exposed to MA were more sensitive to sub-chronic administration of MA in adulthood than prenatally SAL-exposed rats. However, this sensitizing effect of prenatal MA exposure was manifested differently in males and females. In contrast, prenatal MA exposure decreased baseline locomotion in females. This study indicates that gender plays an important role in the sensitivity to MA during prenatal development and in adulthood.
- MeSH
- analýza rozptylu MeSH
- chování zvířat účinky léků MeSH
- krysa rodu Rattus MeSH
- methamfetamin farmakologie MeSH
- potkani Wistar MeSH
- sexuální faktory MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- methamfetamin MeSH
Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test.
- MeSH
- amfetamin škodlivé účinky MeSH
- analýza rozptylu MeSH
- dopaminové látky škodlivé účinky MeSH
- kokain škodlivé účinky MeSH
- krysa rodu Rattus MeSH
- methamfetamin škodlivé účinky MeSH
- modely nemocí na zvířatech MeSH
- operantní podmiňování účinky léků MeSH
- poruchy spojené s užíváním psychoaktivních látek etiologie patofyziologie psychologie MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- tělesná hmotnost účinky léků 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
- práce podpořená grantem MeSH
- Názvy látek
- amfetamin MeSH
- dopaminové látky MeSH
- kokain MeSH
- methamfetamin MeSH
Our previous study showed that single injection of methamphetamine decreases social interaction (SI) in a dose-dependent manner that was further affected by stressful environment conditions. The aim of this study was to examine the effect of methamphetamine and its interaction with gonadal hormones on SI. Adult male and female rats were gonadectomized and assigned to testosterone-treated and oil-treated groups in male rats and estradiol-treated and oil-treated groups in female rats, respectively. Hormones were administered 30 min before each habituation in the open field. All four hormonal groups were further divided to control (without injection), saline (1 ml/kg saline injection), and methamphetamine (1 mg/kg) groups. Injections were applied 30 min before the SI test. The total duration and the total number of SI and nonsocial behavioral patterns were assessed. This study showed that an acute methamphetamine administration in a dose of 1 mg/kg decreased different types of SI in both sexes. In contrast, the same dose of methamphetamine increased locomotion and rearing behavior in male and female rats. The frequency and/or duration of SI (especially mutual sniffing and allogrooming) was lower in adult female rats relative to gonadectomized male rats, but locomotion was increased in female relative to male rats regardless of the presence or absence of gonadal hormones. In conclusion, this study is novel especially because it examines SI in both sexes in relation to the presence or absence of gonadal hormones.
- MeSH
- chování zvířat * MeSH
- estradiol metabolismus farmakologie MeSH
- gonády chirurgie MeSH
- interpersonální vztahy * MeSH
- krysa rodu Rattus MeSH
- lékové interakce MeSH
- lokomoce MeSH
- methamfetamin farmakologie MeSH
- modely u zvířat MeSH
- pohlavní hormony metabolismus farmakologie MeSH
- pohybová aktivita MeSH
- potkani Wistar MeSH
- preklinické hodnocení léčiv MeSH
- sexuální faktory MeSH
- stimulanty centrálního nervového systému farmakologie MeSH
- testosteron metabolismus farmakologie 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
- estradiol MeSH
- methamfetamin MeSH
- pohlavní hormony MeSH
- stimulanty centrálního nervového systému MeSH
- testosteron MeSH
Functional and morphological consequences of ischemic lesions are partially related to the production of reactive oxygen species (ROS). The aim of the study was to create a unilateral photothrombic lesion with minimal morphological changes and minor sensorimotor and cognitive deficits and also to test whether the application of ROS scavengers after the end of induction of ischemia had improved the functional outcome. Adult Wistar male rats were randomly divided into five groups: naive control, sham operated animals, animals with induced ischemia, and two groups of animals with induced ischemia and subsequent ROS scavenger application -melatonin or tempol. The group subjected to ischemia showed a significant decline in performance in sensorimotor tests and the Morris water maze (MWM) test, compared to control animals. Tempol (50 mg/kg, i.p.) did not improve sensorimotor function and did not change spatial learning. Melatonin (100 mg/kg, i.p.), on the contrary, resulted in a significant improvement in animals' performances. All the ischemia subjected animals had increased speed of swimming in the MWM test, compared to the control group. Our findings showed that subsequent application of ROS scavengers improve ischemia outcomes, with melatonin being more potent. Conversely, neither melatonin, nor tempol decreased swimming speed cased by ischemia.
- MeSH
- bludiště - učení MeSH
- časové faktory MeSH
- chování zvířat MeSH
- cyklické N-oxidy farmakologie MeSH
- ischemie mozku patologie MeSH
- ischemie patologie MeSH
- kognice MeSH
- krysa rodu Rattus MeSH
- melatonin farmakologie MeSH
- neuroprotektivní látky farmakologie MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku MeSH
- scavengery volných radikálů * MeSH
- senzorická zpětná vazba MeSH
- spinové značení MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cyklické N-oxidy MeSH
- melatonin MeSH
- neuroprotektivní látky MeSH
- reaktivní formy kyslíku MeSH
- scavengery volných radikálů * MeSH
- spinové značení MeSH
- tempol MeSH Prohlížeč
The effect of psychostimulants on social behavior still remains unclear. Therefore the aim of the present study was to assess the effect of low doses of methamphetamine (MA) on social interaction (SI) in adult male rats. Rats were tested in three environmental conditions: (1) dimly lit, familiar environment, (2) dimly lit, unfamiliar environment and (3) intensely lit, unfamiliar environment considered to be low, middle and high stress, respectively. In each condition different set of animals was used. Rats were always divided into five groups. Control (without injection), saline (with 1 ml/kg saline injection) and three MA groups (doses: 0.5, 1 and 1.5mg/kg). Injections were applied 30 min prior to testing. Always a pair of unfamiliar rats of the same treatment group was tested. Their behavior was video recorded for 5 min in an open field. Times spent by SI (following, climbing, genital investigation, etc.) and non-social behavior (locomotion, rearing) were analyzed using a two-way ANOVA (drug treatment x stress condition). Our data demonstrate that all doses of MA, reduced SI. In addition, the unfamiliarity of the arena increased exploratory behavior (locomotion and rearing) in all treatment groups, while the SI was affected by the environmental condition only in controls or saline-treated rats, but not in MA-treated groups. In conclusion, our data demonstrate that MA administration impairs SI in dose- and stress condition-specific manner, however, some of our results may be due to increase locomotion and rearing induced by MA.
- MeSH
- krysa rodu Rattus MeSH
- methamfetamin farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- psychický stres psychologie MeSH
- sociální chování * MeSH
- stimulanty centrálního nervového systému farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- methamfetamin MeSH
- stimulanty centrálního nervového systému MeSH
Even though it is obvious that glutamate plays an important role in the effect of psychostimulants on seizures, the role of non-NMDA receptors remains uncertain. The aim of the present study was to determine whether acute methamphetamine (MA) administration changes sensitivity to seizures induced with kainic acid in prenatally MA-exposed adult rats. Adult male and female rats (prenatally MA exposed, prenatally saline exposed, and controls) were divided into groups that received a challenge dose (1mg/kg) of MA and groups that did not receive the MA challenge (saline injected). Systemic administration of 15 mg/kg kainic acid was used as a seizure model. Our results demonstrated that a single injection of MA (1mg/kg) affects kainic acid-induced seizures differently depending on prenatal exposure, sex, and female estrous cycle. Even though daily injections of MA (5mg/kg) in maternal rats did not have a long-term effect on susceptibility to seizures induced with kainic acid in adult progeny, sensitivity to the challenge dose of MA differed between the prenatal exposure groups.
- MeSH
- analýza rozptylu MeSH
- estrální cyklus účinky léků MeSH
- incidence MeSH
- krysa rodu Rattus MeSH
- kyselina kainová MeSH
- methamfetamin farmakologie MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- reakční čas účinky léků MeSH
- sexuální faktory MeSH
- stimulanty centrálního nervového systému farmakologie MeSH
- těhotenství MeSH
- záchvaty chemicky indukované diagnóza MeSH
- zpožděný efekt prenatální expozice 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
- práce podpořená grantem MeSH
- Názvy látek
- kyselina kainová MeSH
- methamfetamin MeSH
- stimulanty centrálního nervového systému MeSH
The aim of our study was to examine the effect of prenatal methamphetamine (MA) exposure and cross-fostering on cognitive functions of adult male rats tested in Morris water maze (MWM). Rat mothers were exposed daily to injection of MA (5mg/kg) or saline for 9 weeks: prior to impregnation, throughout gestation and lactation periods. Females without any injections were used as an absolute control. On postnatal day 1, pups were cross-fostered so that each mother raised 4 pups of her own and 8 pups from the mothers with the other two treatments. Four types of tests were used: (1) Place navigation test (Learning), (2) Probe test (Probe), (3) Retention memory test (Memory) and (4) Visible platform task. Our results demonstrate that the prenatal exposure to MA does not impact learning and memory, while postnatal exposure to MA shows impairments in cognition. In the test of learning, all animals fostered to MA-treated dams had longer latencies, bigger search error and used lower spatial strategies than the animals fostered to control or saline-treated mother, regardless of prenatal exposure. Regardless of postnatal exposure, the animals prenatally exposed to saline swam faster in all the tests than the animals prenatally exposed to MA and controls, respectively. This study indicates that postnatal but not prenatal exposure to MA affects learning in adult male rats. However, it is still not clear whether these impairments are due to a direct effect of MA on neuronal structure or due to an indirect effect of MA mediated by impaired maternal care.
- MeSH
- analýza rozptylu MeSH
- bludiště - učení účinky léků MeSH
- časové faktory MeSH
- chování zvířat MeSH
- kognitivní poruchy chemicky indukované MeSH
- krysa rodu Rattus MeSH
- mateřské chování fyziologie MeSH
- methamfetamin škodlivé účinky MeSH
- neuropsychologické testy MeSH
- novorozená zvířata MeSH
- pěstounství psychologie MeSH
- plavání psychologie MeSH
- reakční čas fyziologie MeSH
- retence (psychologie) účinky léků fyziologie MeSH
- rozdělení chí kvadrát MeSH
- stimulanty centrálního nervového systému škodlivé účinky MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice 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
- práce podpořená grantem MeSH
- Názvy látek
- methamfetamin MeSH
- stimulanty centrálního nervového systému MeSH
Methamphetamine is a commonly abused psychostimulant that causes addiction and is often abused by pregnant women. Acute or chronic administration of methamphetamine elevates the levels of the extracellular monoamine neurotransmitters, such as dopamine. The aim of the present study was to show whether prenatal exposure to methamphetamine (5mg/kg, entire gestation) or saline in Wistar rats induces changes in dopamine levels and its metabolites in the nucleus accumbens, and in behavior (locomotor activity, rearing, and immobility) after the administration of a challenge dose of methamphetamine (1mg/kg) or saline in male offspring. We found that adult offspring prenatally exposed to methamphetamine had higher basal levels of dopamine (about 288%), dihydroxyphenylacetic acid (about 67%) and homovanillic acid (about 74%) in nucleus accumbens. An increased basal level of dopamine corresponds to lower basal immobility in offspring prenatally exposed to methamphetamine. The acute injection of methamphetamine in adulthood increased the level of dopamine in the nucleus accumbens, which is related to an increase of locomotion and rearing (exploration). In addition, prenatally methamphetamine-exposed rats showed higher response to the challenge dose of methamphetamine, when compared to prenatally saline-exposed rats. In conclusion, rats exposed to methamphetamine in utero have shown changes in the mesolimbic dopaminergic system and were more sensitive to the administration of the acute dose of methamphetamine in adulthood.
- MeSH
- čas MeSH
- chování zvířat účinky léků fyziologie MeSH
- dopamin metabolismus MeSH
- inhibitory vychytávání adrenergních neurotransmiterů toxicita MeSH
- krysa rodu Rattus MeSH
- kyselina 3,4-dihydroxyfenyloctová metabolismus MeSH
- kyselina homovanilová metabolismus MeSH
- methamfetamin toxicita MeSH
- modely nemocí na zvířatech MeSH
- nervové dráhy účinky léků růst a vývoj patofyziologie MeSH
- nucleus accumbens účinky léků růst a vývoj patofyziologie MeSH
- pátrací chování účinky léků fyziologie MeSH
- pohybová aktivita účinky léků fyziologie MeSH
- tegmentum mesencephali - area ventralis účinky léků růst a vývoj patofyziologie MeSH
- těhotenství MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zpožděný efekt prenatální expozice metabolismus patologie 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
- práce podpořená grantem MeSH
- Názvy látek
- dopamin MeSH
- inhibitory vychytávání adrenergních neurotransmiterů MeSH
- kyselina 3,4-dihydroxyfenyloctová MeSH
- kyselina homovanilová MeSH
- methamfetamin MeSH
The aim of our study was to reveal whether acute methamphetamine (MA) administration changes the sensitivity to seizures induced by N-methyl-D-aspartate (NMDA) in prenatally MA-exposed adult rats. Adult rats with respect to sex and female estrous cycle (prenatally MA-exposed, prenatally saline-exposed, and controls) were divided into groups with acute MA (1 mg/kg) or without acute drug administration (saline injection). Intraperitoneal administration of 250 mg/kg of NMDA was used as a seizure model. The present study demonstrated that both prenatal MA and prenatal saline exposure decreased the latency to onset of stereotypy and clonic-tonic seizures. Acute MA administration decreased latency to onset of stereotypic behavior in all groups, while increased latency to onset of clonic-tonic seizures in prenatally saline-exposed rats. The duration of NMDA seizures was longer after acute MA administration relative to animals without acute MA pretreatment in both control groups. In addition, males displayed decreased susceptibility to NMDA-induced seizures relative to females regardless of their estrous cycle. Our study suggests that acute MA exposure changes susceptibility to NMDA-induced seizures in respect of prenatal exposure and sex. However, it seems that the effect of prenatal exposure is not induced by the drug per se but rather by the repeated injection exposure that causes prenatal stress.
- MeSH
- agonisté excitačních aminokyselin aplikace a dávkování toxicita MeSH
- časové faktory MeSH
- estrální cyklus fyziologie MeSH
- krysa rodu Rattus MeSH
- methamfetamin farmakologie MeSH
- N-methylaspartát aplikace a dávkování toxicita MeSH
- potkani Wistar MeSH
- rozvrh dávkování léků MeSH
- sexuální faktory MeSH
- stereotypní chování účinky léků MeSH
- stimulanty centrálního nervového systému farmakologie MeSH
- těhotenství MeSH
- záchvaty chemicky indukované MeSH
- zpožděný efekt prenatální expozice MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- agonisté excitačních aminokyselin MeSH
- methamfetamin MeSH
- N-methylaspartát MeSH
- stimulanty centrálního nervového systému MeSH