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ABSTRACT: The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to challenge dose of cocaine or morphine. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge doses of saline (1 ml/kg), cocaine (5 mg/kg) or morphine (5 mg/kg). Behavior in unknown environment was examined in Laboras, nociception in Plantar test, and active drug-seeking behavior in conditioned place preference (CPP). Our data demonstrate that cocaine increased the exploratory activity in Laboras test in prenatally saline-exposed, but decreased it in prenatally MA-exposed rats. An analgesic effect of cocaine was demonstrated only by the tail withdrawal and it was independent of the prenatal drug exposure. CPP test showed that prenatal MA exposure induced rather tolerance than sensitization to cocaine. In contrast to cocaine effects, morphine decreased rearing activity in both, prenatally MA-exposed and saline-exposed rats, and locomotion only in prenatally MA-exposed rats in the Laboras. In the Plantar test, the results demonstrated that morphine had an analgesic effect in prenatally saline-exposed rats but this effect was suppressed in prenatally MA-exposed rats. In the CPP test morphine induced drug-seeking behavior, which however was not affected by prenatal drug exposure. Thus, our data demonstrate that there is a cross-effect between prenatal MA exposure and the challenge dose of other drug in adulthood, however drug-seeking behavior is not increased by prenatal MA exposure as we expected.
Prague medical report 01/2012; 113(3):189-205.
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ABSTRACT: The aim of the present study was to investigate the impact of prenatal and postnatal methamphetamine (MA) exposure on behavior and anxiety in adult male and female rats. Mothers were daily exposed to injection of MA (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother raised 6 saline-exposed pups and 6 MA-exposed pups. Based on the prenatal and postnatal exposure 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in the Open field (OF) and in the Elevated plus maze (EPM) in adulthood. Locomotion, exploration, immobility and comforting behavior were evaluated in the OF, while anxiety was assessed in the EPM. While prenatal MA exposure did not affect behavior and anxiety in adulthood, postnatal MA exposure (i.e. MA administration to lactating mothers) induced long-term changes. Specifically, adult female rats in diestrus and adult males postnatally exposed to MA via breast milk (S/MA and MA/MA) had decreased locomotion and exploratory behavior in the OF and showed increased anxiety-like behavior in the EPM when compared to female rats in diestrus or males postnatally exposed to saline (S/S and MA/S). In adult females in proestrus, postnatal exposure to MA affected only exploratory behavior in the OF when compared to rats in proestrus postnatally exposed to saline. Thus, the present study shows that postnatal exposure to MA via breast milk impairs behavior in unfamiliar environment and anxiety-like behavior of adult male and female rats more than prenatal MA exposure.
Physiology & Behavior 08/2011; 105(2):364-70. · 2.87 Impact Factor
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ABSTRACT: Methamphetamine is a psychostimulant drug which causes the release of monoamine neurotransmitters. Although drugs of abuse are known to have analgesic effects, there is a lack of evidence regarding the effect of prenatal exposure to methamphetamine on nociception in adulthood. Adult Wistar rats whose mothers had received daily exposure to methamphetamine (5 mg/kg; s.c.) or saline, during gestation or gestation and lactation periods, were examined for: (1) gender differences in nociception; (2) an association between nociception and gross-motor behavior in the plantar test; (3) effects of cross-fostering on nociception; and (4) analgesic effects of an acute injection of methamphetamine (1 mg/kg s.c.). Nociception was tested using the plantar test on postnatal days 85-90. Prenatal methamphetamine increased sensitivity to pain on forelimbs (p<0.0001) and hind limbs (p<0.05) in females only. Prenatal methamphetamine treated male rats fostered by adoptive injection stressed mothers had higher sensitivity to pain than prenatally injection stressed rats fostered by methamphetamine treated mothers (p<0.05). Acute methamphetamine induced analgesia faster in prenatally methamphetamine exposed rats than in controls. In all groups, analgesia increased in the cranio-caudal direction (p<0.0001). From our behavioral data it can be concluded that exposure to methamphetamine during the prenatal period completely dissociates the relationship between nociception and intensity of overall behavior observed in intact animals in adulthood. Thus, our results indicate that perinatal exposure to psychostimulants may have long-term impact on several functions related to dopaminergic system.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 02/2011; 29(1):85-92. · 2.03 Impact Factor
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ABSTRACT: There are only few studies that examine the effect of prenatal methamphetamine (MA) exposure on the sensitivity to the same drug and the drug-seeking behavior in adulthood. The aim of the present study was to examine the effect of prenatal MA exposure on exploratory behavior and nociception with respect to challenge dose of the same drug. Mothers of the tested offspring received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge dose of MA (1 mg/kg) or saline. A modified Open field test (Laboras) was used to examine behavior in unknown environment. Plantar test was used to measure nociception on forelimbs, hind limbs, and the tail. Conditioned place preference (CPP) test was used to examine drug-seeking behavior. Our results in Laboras demonstrated that prenatal MA exposure sensitized the animals to the challenge dose of MA. Specifically prenatally MA-exposed animals that received the challenge MA in adulthood displayed higher locomotion and rearing activity relative to all the other groups. The Plantar test data suggest analgesic effect of MA (1 mg/kg), which however, did not differ based on the prenatal drug exposure. The results of CPP test showed that MA (5 mg/kg) conditioning resulted in increased drug-seeking behavior, but this effect was not affected by prenatal drug exposure. Thus, our data demonstrate that the effects of prenatal MA exposure and the challenge dose of the same drug in adulthood depend on behavioral model used.
Prague medical report 01/2011; 112(2):102-14.
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ABSTRACT: Our previous studies repeatedly demonstrated that prenatal methamphetamine (MA) exposure alters seizure susceptibility in adult rats. Both the inhibitory GABA system and the excitatory NMDA system play a role in the effect of MA on epileptic seizures. On the basis of our previous behavioral results, the effect of cross-fostering on seizure susceptibility in adult female rats was examined in the present study. Bicuculline (GABA(A) receptor antagonist) and NMDA (NMDA receptor agonist) were used to induce seizures in adult female offspring exposed to MA in the prenatal and/or preweaning periods. Female dams were injected with MA (5mg/kg daily) or physiological saline (S) for approximately 9 weeks [about 3 weeks prior to impregnation, for the entire gestation period (22 days), and in the preweaning period (21 days)]. Absolute controls (C) did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received pups from all three treatments. Thus, nine groups (based on the prenatal and postnatal drug exposures) of adult female rats were tested in each seizure test: C/C, C/S, C/MA, S/C, S/S, S/MA, MA/C, MA/S, MA/MA. The present study demonstrated that both the excitatory NMDA system and the inhibitory GABA system are involved in the proconvulsive effect of MA during prenatal and partially also postnatal development in female rats. However, because our results did not show any improvement in seizure susceptibility in prenatally MA-exposed animals that were fostered by control mothers (MA/C) relative to their siblings fostered by MA-treated mothers (MA/MA), our hypothesis of the cross-fostering effect seems to be incorrect in contrast to our behavioral studies.
Epilepsy & Behavior 11/2010; 20(1):6-11. · 2.34 Impact Factor
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ABSTRACT: Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory gamma-aminobutyric acid (GABA) and excitatory N-methyl-D-aspartate (NMDA) systems play a role in the effect of stimulants in the genesis of epileptic seizures. Our previous studies showed that prenatal methamphetamine (MA) exposure induced long-term changes in seizure susceptibility. The aim of the present study was to investigate the effect of cross-fostering on the prenatal and postnatal MA-exposed rats, respectively, on their seizures in adulthood. Bicuculline (GABA(A) receptor antagonist), NMDA (NMDA receptor agonist) and flurothyl (a convulsant gas) were used to induce seizures in adult male offsprings. Female dams were injected with MA (5 mg/kg daily) or physiological saline (S) for approx. 9 week [about 3 week prior to impregnation, for the entire gestation period (22 days) and in preweaning period (21 days)]. Absolute controls (C) did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received pups from all three treatments. Thus, nine groups (based on the prenatal and postnatal drug exposure) of adult male rats were tested in each seizure test: C/C; C/S; C/MA; S/C; S/S; S/MA; MA/C; MA/S; MA/MA. The present study demonstrates that the effect of prenatal and/or postnatal MA exposure is seizure model specific. In addition, our data show that there is an effect of cross-fostering on seizures; particularly, the effect of prenatal MA exposure shown in animals fostered by control mothers is no longer apparent in animals fostered postnatally by MA-treated mothers. Such effect of postnatal treatment is not manifested in prenatal controls. In summary, it seems that: (1) prenatal MA exposure alters seizure susceptibility more than postnatal MA exposure; (2) especially in seizures induced by chemicals that affect GABAergic system (bicuculline, flurothyl) notable effect of adoption (cross-fostering) is apparent; (3) in seizure models that are associated with NMDA system (NMDA, flurothyl), effect of prenatal stress seems to play a role.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 10/2010; 28(6):429-35. · 2.03 Impact Factor
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ABSTRACT: Methamphetamine (MA) is a drug causing potent psychomotor activation. The aim of the present study was: (1) to assess the effect of prenatal and acute MA administration on behavior in adult male rats and (2) to find out if the prenatal exposure to MA increases sensitivity to acute MA application in adulthood. Behavior of adult male rats prenatally exposed to MA (5mg/kg) or saline was tested in Open field (OF) and Elevated plus maze (EPM). Subcutaneously administered MA (1mg/kg) or saline were used as challenge in adulthood, 30 min prior to testing. Our results showed that prenatal MA did not have an effect on baseline behavior in either of the tests. By contrast, acute MA increased overall psychomotor activity by increasing locomotion and exploratory behavior and decreasing comforting behavior. Moreover, adult rats prenatally exposed to MA exhibited increased sniffing and decreased rearing after acute MA dose in adulthood relative to prenatally saline-exposed rats. In addition, while acute MA application decreased anxiety in rats prenatally exposed to MA, rats prenatally exposed to saline were less sensitive to the anxiolytic effects of MA. Our results indicate that changes caused by prenatal exposure to psychostimulants may become apparent as different reactivity to drugs of abuse when an individual encounters them later in life. In addition, we found that the anxiolytic effect of acute MA (1mg/kg) probably depends also on the reactivity to stress and the activity of hypothalamo-pituitary-adrenal axis.
Physiology & Behavior 12/2009; 99(3):381-7. · 2.87 Impact Factor
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ABSTRACT: Psychostimulants have been shown to alter behaviour in both rats and humans. The aim of the present study was: (1) to assess the effect of prenatal and acute methamphetamine (MA) administration on behaviour in adult male rats and (2) to find out if the prenatal exposure to MA increases sensitivity to acute MA application in adulthood. Behaviour of adult male rats prenatally exposed to MA (5 mg/kg) or no drug was tested in Open field (OF) and Elevated plus maze (EPM). Half of the animals were injected with MA (1 mg/kg) subcutaneously 30 minutes prior to testing. Locomotion, exploration, comforting behaviour and anxiety were evaluated in the OF, while anxiety and exploratory behaviour were assessed in the EPM. Our results showed that prenatal MA did not have an effect on baseline behaviour in either of the tests. By contrast, acute MA increased overall psychomotor activity by increasing locomotion and exploratory behaviour and decreasing comforting behaviour. Moreover, adult rats prenatally exposed to MA were more sensitive to the effects of acute MA on exploration. In addition, acute MA application decreased anxiety in the OF as well as in the EPM. Our present study, thus, demonstrates that acute MA increases overall psychomotor activity and decreases anxiety to novel environment. To further support our hypothesis that prenatal MA exposure increases sensitivity to drugs in adulthood, studies investigating the levels of dopamine in the rat brain after prenatal MA exposure are planned.
Prague medical report 02/2009; 110(1):67-78.
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ABSTRACT: Our previous studies demonstrated that methamphetamine administered during gestation and lactation periods impairs maternal behavior, alters the functional development of rat pups and affects behavior in adulthood. The aim of our study was to investigate the effect of prenatal methamphetamine exposure and cross-fostering on learning tested in Morris water maze (MWM) in adult male rats. Mothers were daily exposed to injection of methamphetamine (MA) (5 mg/kg) or saline (S): prior to impregnation and throughout gestation and lactation periods. On postnatal day 1, pups were cross-fostered so that each mother received some of her own and some of the pups of mother with the opposite treatment. Based on the prenatal and postnatal treatments 4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in MWM. Two types of tests were used: (1) "Place navigation test" (Learning) and (2) "Probe test" (Probe). In the test of learning, all animals fostered by methamphetamine-treated dams had longer latencies and trajectories, and bigger search error than the animals fostered by saline-treated control mother, regardless of prenatal exposure. Further, the animals prenatally exposed to methamphetamine swam slower than the animals prenatally exposed to saline, regardless of postnatal exposure in the test of learning and in the Probe test. Our results showed that neither prenatal nor postnatal methamphetamine exposure affected the Probe test. Our results showed that prenatal exposure to methamphetamine at dose of 5 mg/kg does not impair learning in the MWM, while postnatal exposure to methamphetamine from mothers' breastmilk and maternal care of mother exposed to methamphetamine impairs learning of adult male rats. On the other hand, the maternal care of control mothers does not impair learning of rat pups prenatally exposed to methamphetamine. The present study demonstrates that cross-fostering may affect learning in adulthood.
Prague medical report 02/2009; 110(3):191-200.
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ABSTRACT: The aim of the present study was to investigate the impact of prenatal methamphetamine (MA) exposure and application of the same drug in adulthood on cognitive functions of adult male rats tested in Morris water maze (MWM). Adult male rats prenatally exposed to MA (5 mg/kg), saline or no injection were examined. Half of the animals were injected daily with MA (1 mg/kg) after finishing the testing. Three types of tests were used: (1) "Place navigation test" (Learning), (2) "Probe test" and (3) "Retention memory test" (Memory). Our results showed that prenatal MA exposure did not affect the test of learning and the Probe test. In the test of memory prenatally MA-exposed rats showed smaller search errors and used spatial strategies more than both control groups. Further, MA application in adulthood prolonged trajectories, increased the incidence of random search and decreased the incidence of direct swim in the Place navigation test. In addition, MA administration in adulthood increased the speed of swimming regardless of prenatal exposure. The present study thus demonstrates that 1) Prenatal MA exposure does not affect learning in the MWM, 2) Prenatal MA exposure improves performance in the Retention memory test in the MWM, and 3) MA application in adulthood impairs learning in the Morris water maze.
Physiological research / Academia Scientiarum Bohemoslovaca 12/2008; 58(5):741-50. · 1.55 Impact Factor
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ABSTRACT: This review, which summarizes our findings concerning the long-term effects of pre-, peri- and postnatal factors affecting development, nociception and sensorimotor functions, focuses on three areas: 1) perinatal factors influencing nociception in adult rats were examined in rats with hippocampal lesions, after the administration of stress influencing and psychostimulant drugs (dexamethasone, indomethacine and methamphetamine); 2) the effect of pre- and early postnatal methamphetamine administration was shown to impair the development of sensorimotor functions tested in rat pups throughout the preweaning period; 3) the effect of extensive dorsal rhizotomy of the brachial plexus during the early postnatal period was studied with respect to neuropathic pain development and sensorimotor functions. The present study indicates that prenatal or neonatal stress, as well as various drugs, may disturb the development of the nociceptive system and cause long-term behavioral changes persisting to adulthood and that some types of neuropathic pain cannot be induced during the first two postnatal weeks at all. A mature nervous system is required for the development of the described pathological behaviors.
Physiological research / Academia Scientiarum Bohemoslovaca 06/2008; 57 Suppl 3:S79-88. · 1.55 Impact Factor
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Ceskoslovenska fysiologie / Ustredni ustav biologicky 02/2008; 57(4):133-8.
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ABSTRACT: Our previous studies demonstrated that methamphetamine (MA) administered during gestation and lactation periods impairs maternal behavior as well as the postnatal development of rat pups. The present study tested the hypothesis that the cross-fostering influences the development of rat pups. Mothers were daily exposed to injection of MA (5 mg/kg) and saline for 9 weeks: three weeks prior to impregnation, throughout the entire gestation period and during lactation. As a control (C) females with no injections were used. On postnatal day (PD 1), pups were cross-fostered so that each mother received some of her own and some of the pups of mother with the other treatments. Pup's development and sensorimotor coordination was examined between PD 1 and PD 23. Following tests were used: tail pull (PD 10), righting reflex on surface (PD 12), righting reflex on mid-air (PD 17) and rotarod (PD 23). Our results showed that the birth weight in prenatally MA-exposed pups was lower than controls or saline-exposed pups regardless of sex. Prenatally MA-exposed pups gained less weight than controls or saline-exposed pups regardless of postnatal treatment and sex. Further, our data demonstrated that prenatal and postnatal MA exposure impairs sensorimotor functions. On the other hand, postnatal care of control mothers at least partially suppressed the negative effect of prenatal MA exposure. Our hypothesis, that the cross-fostering may affect postnatal development of pups, was confirmed. Our results support the hypothesis that variation in rat maternal care could serve as a mechanism for a non-genomic behavioral mode of transmission of traits.
Prague medical report 02/2008; 109(1):50-61.
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ABSTRACT: Studies showed that stimulant drugs that affect the monoaminergic system alter both behavioral and cognitive processes. The aim of the present study was to investigate the impact of prenatal and acute methamphetamine (MA) exposure on cognitive functions of adult male rats tested in Morris water maze (MWM). We tested adult male rats prenatally exposed to MA (5 mg/kg), saline or no injection. Half of the animals were injected daily with MA (1 mg/kg) after finishing the testing. All injections were administered subcutaneously. Three types of tests were used: (1) "Place navigation test" (Learning), (2) "Probe test" (Probe) and (3) "Retention memory test" (Memory). Our results showed that prenatal MA exposure did not affect the test of learning and the Probe test. In the test of memory prenatally MA-exposed rats had lower latencies than animals prenatally exposed to saline. Further, acute MA administration increased the speed of swimming in all rats regardless of prenatal drug exposure and the type of test and, however, the increase in the speed was significantly greater in rats prenatally exposed to MA than in rats without any prenatal exposure. In addition, acute MA application significantly prolonged trajectories in the Place navigation test. The present study thus demonstrates that: (1) Prenatal MA exposure does not affect learning in the MWM. (2) Prenatal MA exposure increases the sensitivity to acute drug injection. (3) Acute MA application impairs learning in the MWM.
Prague medical report 02/2008; 109(1):62-70.
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ABSTRACT: Methamphetamine (MA) is a drug causing potent psychomotor activation. The aim of the present study was: (1) to assess the effect of prenatal and acute MA administration on behavior in adult male rats and (2) to find out if the prenatal exposure to MA increases sensitivity to acute MA application in adulthood.Behavior of adult male rats prenatally exposed to MA (5 mg/kg) or saline was tested in Open field (OF) and Elevated plus maze (EPM). Subcutaneously administered MA (1 mg/kg) or saline were used as challenge in adulthood, 30 min prior to testing.Our results showed that prenatal MA did not have an effect on baseline behavior in either of the tests. By contrast, acute MA increased overall psychomotor activity by increasing locomotion and exploratory behavior and decreasing comforting behavior. Moreover, adult rats prenatally exposed to MA exhibited increased sniffing and decreased rearing after acute MA dose in adulthood relative to prenatally saline-exposed rats. In addition, while acute MA application decreased anxiety in rats prenatally exposed to MA, rats prenatally exposed to saline were less sensitive to the anxiolytic effects of MA.Our results indicate that changes caused by prenatal exposure to psychostimulants may become apparent as different reactivity to drugs of abuse when an individual encounters them later in life. In addition, we found that the anxiolytic effect of acute MA (1 mg/kg) probably depends also on the reactivity to stress and the activity of hypothalamo-pituitary-adrenal axis.
Physiology & Behavior.
