Increased seizure susceptibility induced by prenatal methamphetamine exposure in adult female rats is not affected by early postnatal cross-fostering (original) (raw)
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Effect of cross-fostering on seizures in adult male offspring of methamphetamine-treated rat mothers
International Journal of Developmental Neuroscience, 2010
Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory ␥-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;
Seizure susceptibility in prenatally methamphetamine-exposed adult female rats
Brain Research, 2005
The purpose of the present study was to examine the effect of prenatal methamphetamine (MA) exposure on seizures induced by bicuculline and N-methyl-d-aspartate in adult female rats. The present results show that prenatal MA exposure alters seizures in a modelspecific manner and that the seizure susceptibility of adult female rats may be affected by the stage of their estrous cycle.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2009
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.
Epilepsy Research, 2008
The aim of the present study was to investigate whether sensitivity to flurothyl seizures after an acute methamphetamine (MA) administration is different in prenatally MAexposed adult rats than in controls without prenatal drug exposure. Adult male and female rats exposed prenatally to MA (5 mg/kg), saline or neither (controls) were divided into groups; one group received acute MA (1 mg/kg s.c.) injection and the other group received saline. Rats were then challenged with flurothyl at a constant flow rate to induce seizures. The threshold of the first focal clonus, clonic seizures and tonic-clonic seizures were analyzed. Effects of prenatal drug exposure: In animals without acute MA administration prior to seizure testing, prenatal MA exposure decreased threshold of the first clonus relative to control animals. This decrease in threshold was not apparent in groups pretreated with acute MA injection. Effects of acute MA administration: There was an increased threshold to both, first focal clonus and clonic seizures in animals with acute MA injection than in animals without it. The increase induced by acute MA pretreatment was higher in prenatally MA-exposed animals relative to controls. Further, clonic seizures were shorter and developed faster into tonic-clonic seizures in these acutely injected animals compared to animals without acute MA injection. Effects of hormones: The threshold of all measured attributes was decreased in males. Estrous cycle influences did not lead to changes between groups of prenatal exposure or acute MA administration. Threshold of tonic-clonic seizures was increased in females in proestrus/estrus stage of the estrous cycle relative to diestrous females. Our study suggests that prenatal MA exposure affects the sensitivity of adult rats to the effect of acute MA treatment prior to flurothyl seizures relative to controls.
Neuroscience, 2014
Our previous study demonstrated that chronic prenatal methamphetamine (MA) exposure and a single dose of MA in adulthood decrease focally induced epileptiform activity in adult male rats. As seizures are known to be dependent on sex and female estrous cycle, the goal of the present study was to examine the combined effect of prenatal MA exposure (5 mg/kg) and the MA challenge dose (1 mg/kg) in adulthood on electroencephalography (EEG) recordings and consequences of brain stimulation in freely moving adult female rats with respect to the estrous cycle. Overall, 12 groups of adult female rats were tested: prenatally MA-exposed, prenatally saline-exposed and rats without prenatal injections, each of these groups was either postnatally challenged with MA or with saline injection (MA-MA, MA-S; S-MA, S-S; C-MA, C-S) and further divided according to the stage of the estrous cycle to metestrus/ diestrus (M/D) or proestrus/estrus (P/E). Seizures were induced by repetitive electrical stimulation (15 s/8 Hz) of sensorimotor cortex. Stimulation threshold, duration of afterdischarges (ADs), and presence and duration of spontaneous ADs (SADs) were evaluated. Additionally, behavior associated with stimulation and ADs, and occurrence of wet-dog-shakes (WDS) were analyzed. The present study demonstrates that the prenatal MA exposure decreased the seizure threshold in females in M/D, but not in females in P/E. In addition, prenatally MA-exposed M/D females injected with saline in adulthood had increased the duration of ADs as well as SADs. The challenge dose of MA also decreased the seizure threshold. Moreover, prenatal as well as adult MA administration decreased the number and occurrence of WDS, respectively. Thus, the present study demonstrates that the effect of prenatal MA exposure and challenge dose of the same drug on focally induced epileptiform activity in adult female rats depends on the estrous cycle. Ó
Experimental Neurology, 2011
Administration of psychostimulants is often associated with increased seizure susceptibility. In our previous studies prenatal methamphetamine (MA) exposure increased seizure susceptibility of adult rats in models of primarily or secondarily generalized seizures induced by convulsant drugs. The effect of a single MA challenge dose in adulthood on chemically induced generalized seizures however, depends on the prenatal MA exposure history. Thus, the present study used a model of focal electrical stimulation to determine whether prenatal MA exposure with or without the adult challenge MA dose has the same outcome in a focal seizure model. Total of six groups of adult male rats were tested (prenatally MA-exposed, prenatally saline-exposed and rats without prenatal injections), each of these groups was either postnatally challenged with MA or with vehicle injection (MA-MA, MA-S; S-MA, S-S; C-MA, C-S). Seizures were induced by repetitive electrical stimulation (15 s/8 Hz) of sensorimotor cortex. Stimulation threshold, duration of afterdischarges (ADs), and presence and duration of spontaneous ADs (SAD) were evaluated. Additionally, behaviors associated with stimulation and ADs, and occurrence of wet-dog shakes (WDS) were analyzed. Our data demonstrate that daily injection of MA (5 mg/kg) within prenatal period decreased the occurrence of WDS and SADs, and shortened the duration of ADs and SADs suggesting anticonvulsant effects. Moreover, the challenge dose of MA (1 mg/kg) increased seizure threshold in all groups of rats, shortened duration of ADs in controls and prenatally saline-exposed animals, shortened duration of SADs in prenatally saline-exposed rats and totally eliminated WDS in all groups. Thus, the present study demonstrates that both chronic prenatal MA exposure and a single dose of MA in adulthood decrease focally induced epileptiform activity in adult male rats.
Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?
Behavioural Brain Research, 2011
The aim of the present study was to investigate whether sensitivity to flurothyl seizures after an acute methamphetamine (MA) administration is different in prenatally MAexposed adult rats than in controls without prenatal drug exposure. Adult male and female rats exposed prenatally to MA (5 mg/kg), saline or neither (controls) were divided into groups; one group received acute MA (1 mg/kg s.c.) injection and the other group received saline. Rats were then challenged with flurothyl at a constant flow rate to induce seizures. The threshold of the first focal clonus, clonic seizures and tonic-clonic seizures were analyzed. Effects of prenatal drug exposure: In animals without acute MA administration prior to seizure testing, prenatal MA exposure decreased threshold of the first clonus relative to control animals. This decrease in threshold was not apparent in groups pretreated with acute MA injection. Effects of acute MA administration: There was an increased threshold to both, first focal clonus and clonic seizures in animals with acute MA injection than in animals without it. The increase induced by acute MA pretreatment was higher in prenatally MA-exposed animals relative to controls. Further, clonic seizures were shorter and developed faster into tonic-clonic seizures in these acutely injected animals compared to animals without acute MA injection. Effects of hormones: The threshold of all measured attributes was decreased in males. Estrous cycle influences did not lead to changes between groups of prenatal exposure or acute MA administration. Threshold of tonic-clonic seizures was increased in females in proestrus/estrus stage of the estrous cycle relative to diestrous females. Our study suggests that prenatal MA exposure affects the sensitivity of adult rats to the effect of acute MA treatment prior to flurothyl seizures relative to controls.
Epilepsy & Behavior, 2010
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 (1 mg/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 (1 mg/kg) affects kainic acid-induced seizures differently depending on prenatal exposure, sex, and female estrous cycle. Even though daily injections of MA (5 mg/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.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2009
There are studies showing that drug abuse during pregnancy may have a long-term effect on progeny of drug-abusing mothers. Our previous work demonstrated that prenatal and/or postnatal methamphetamine injections impair maternal behavior. The purpose of the present study was to assess the effect of prenatal methamphetamine or stress exposure and postnatal breeding on postnatal development of rat pups. Female rats were injected with methamphetamine (5 mg/kg daily) or physiological saline prior, during and after gestation. Absolute controls did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received some of her own and some of the pups from the mothers with the other two treatments. Pups were weighted daily for the entire lactation period. Postural motor reaction development was examined daily by righting reflex between postnatal day 1 and 12. On postnatal day 15 homing test examining pups' nest-seeking behavior was performed. On postna...
Postnatal development of rat pups is altered by prenatal methamphetamine exposure
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2006
There are studies showing that drug abuse during pregnancy may have impairing effect on progeny of drug-abusing mothers. Methamphetamine (MA) is one of the most common illicit drugs throughout the world. The purpose of the present study was to assess the effect of prenatal MA exposure on postnatal development of rat pups before the time of separation from their mothers. Female rats were injected with MA (5 mg/kg daily) for the duration of their pregnancy. Pups were then tested throughout the lactation period. They were weighed daily and the ano-genital distance was measured on postnatal day (PD) 1. Development of postural motor reaction was tested by righting reflex on surface between PD 1 and 12, and righting reflex in mid-air after PD 12 until successfully accomplished. On PD 15 homing test was examined as a test of pup acute learning. On PD 23 sensory-motor coordination was examined using the rotarod and bar-holding tests. Additionally, the markers of physical maturation, such as eye opening, testes descent in males and vaginal opening in females were also recorded. The birth weight in prenatally MA-exposed pups was lower than in controls or saline-exposed pups regardless of sex. There were no changes induced by prenatal MA exposure in weight gain or in sexual maturation. In righting reflexes, we demonstrated that pups exposed prenatally to MA were slower in righting reflex on surface and that they accomplished the test of righting reflex in mid-air later than controls or saline-exposed pups. The performance of homing test was not affected by prenatal drug exposure. The sensory-motor coordination was impaired in prenatally MAexposed pups when testing in the rotarod test. Also, the number of falls in the bar-holding test was higher in MA-exposed pups than in controls. There were no sex differences in any measures. Thus, the present study demonstrated that prenatal MA exposure impairs development of postural motor movements of rat pups during the first 3 weeks after birth, while not affecting physical or sexual maturation. D