Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats? (original) (raw)
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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
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.
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.
Epilepsy & Behavior, 2011
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 crossfostering 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 (5 mg/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 MAexposed animals that were fostered by control mothers (MA/C) relative to their siblings fostered by MAtreated mothers (MA/MA), our hypothesis of the cross-fostering effect seems to be incorrect in contrast to our behavioral studies.
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.
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;
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.
Experimental Neurology, 2006
The substantia nigra pars reticulata (SNR) plays an important age- and sex-specific role in control of clonic seizures. Its involvement in control of tonic-clonic seizures is contradictory. We investigated the role of the SNR in the tonic-clonic seizures induced in male, female and neonatally castrated male rats using flurothyl. In adult female rats, vaginal impedance determined the changes in progesterone/estrogen ratio. Rats at various postnatal ages received infusions of muscimol or vehicle in the SNRanterior or SNRposterior. Furthermore, in 15-day-old (P15) and adult male rats, ZAPA (a GABA(A) receptor agonist) or AP7 (an NMDA receptor antagonist) was infused. The developmental profile of tonic-clonic seizure threshold differed between male and female rats possibly due to early postnatal testosterone surge in male rats. On the other hand, changing estrogen/progesterone ratio in cycling adult female rats had no effect on seizure threshold. Intranigral muscimol had proconvulsant effects on tonic-clonic seizures only in immature rats, and this effect was dependent on the perinatal testosterone surge. ZAPA had anticonvulsant effects in P15 rats but was not effective in adult rats. Only AP7 had anticonvulsant effects in both adult and P15 rats. Results indicate that thresholds for flurothyl-induced tonic-clonic seizures develop under the control of postnatal testosterone. Although GABAergic inhibition in the SNR affects tonic-clonic seizures in developing rats, only the NMDA antagonist had consistent anticonvulsant effects throughout development.
Prenatal Methotrexate Exposure Decreases Seizure Susceptibility in Young Rats of Two Strains
Experimental Neurology, 2000
Effects of prenatal exposure to methotrexate (MTX) administered in Sprague-Dawley (one 5 mg/kg dose of MTX on gestational day 15; E15) or Wistar (one 5 mg/kg dose of MTX on E14 or E15 or two such doses on E15) pregnant rat dams were studied in developing offspring. Young Sprague-Dawley rats were subjected to rapid kindling on postnatal days (PN) 15 and 16, and to flurothyl seizures on PN 15 and PN 30. Offspring of the Wistar strain were tested in flurothyl on PN 30. In Sprague-Dawley rats, prenatal exposure to MTX decreased susceptibility to kindling-induced seizures on PN 15 and to flurothyl-induced clonic seizures on PN 30. In Wistar rats, a single dose of MTX on E15 was ineffective, but two doses significantly decreased susceptibility to flurothyl-induced seizures. Additionally, due to a shorter duration of pregnancy in Wistar rats, exposure to a single dose of MTX on E14 also decreased susceptibility to flurothyl seizures. MTX, as folic acid antagonist, interferes with DNA synthesis. However, unlike other treatments that suppress DNA synthesis (such as methylazoxymethanol exposure or X-ray radiation), MTX exposure results in anticonvulsant effects in surviving offspring. The data suggest that not all prenatal impairments of DNA have proconvulsant features postnatally. 2000 Academic Press