Attention-deficit/hyperactivity disorder (ADHD) is a mental disorder with a heterogeneous origin with a global incidence that continues to grow. Its causes and pathophysiological mechanisms are not fully understood. It includes a combination of persistent symptoms such as difficulty in concentration, hyperactivity and impulsive behavior. Maternal methamphetamine (MA) abuse is a serious problem worldwide, it can lead to behavioral changes in their offspring that have similarities with behavioral changes seen in children with ADHD. There are several types of ADHD animal models, e.g. genetic models, pharmacologically, chemically and exogenously induced models. One of the exogenously induced ADHD models is the hypoxia-induced model. Our studies, as well as those of others, have demonstrated that maternal MA exposure can lead to abnormalities in the placenta and umbilical cord that result in prenatal hypoxia as well as fetal malnutrition that can result in irreversible changes to experimental animals. Therefore, the aim the present study was to compare the cognitive impairments in MA exposure model with those in established model of ADHD – prenatal hypoxia model, to test whether MA exposure is a valid model of ADHD. Pregnant Wistar rats were divided into four groups based on their gestational exposure to MA: (1) daily subcutaneous injections of MA (5 mg/kg), (2) saline injections at the same time and volume, (3) daily 1-hr hypoxia (10 % O2), and (4) no gestational exposure (controls). Male rat offspring were tested for short-term memory in the Novel Object Recognition Test and the Object Location Test between postnatal days 35 and 40. Also their locomotor activity in both tests was measured. Based on the present results, it seems that prenatal MA exposure is not the best animal model for ADHD since it shows corresponding symptoms only in certain measures. Given our previous results supporting our hypothesis, more experiments are needed to further test possible use of prenatal MA exposure as an animal model of the ADHD.
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., B. Schutová ... [et al.]., and Obsahuje seznam literatury
The present study examined the hypothesis that the extension of noxious effect of methamphetamine (MA) on maternal behavior and postnatal development on the pups may differ in dependence with time of application. Female rats were injected with MA (5 mg/kg) or saline during first (embryonic day (ED) 1-11) or second (ED 12-22) half of gestation. Our results demonstrated that MA exposure on ED 12-22 led to decreased birth weight and weight gained during lactation period relative to rats treated on ED 1-11. Both sexes treated prenatally with MA on ED 1-11 opened eyes earlier compared to animals treated on ED 12-22. As a matter of sensorimotor development application of MA on ED 1-11 impaired the righting reflex, while MA exposure on ED 12-22 impaired the performance of beam balance test in male rats. There were no differences in maternal behavior. Therefore, it seems that MA exposure in the first half of the gestation impaired the early sensorimotor development that is under control of the brain stem, while the MA exposure in the second half of gestation affected the beam balance performance that is dependent on the function of the cerebellum., M. Malinová-Ševčíková, I. Hrebíčková, E. Macúchová, E. Nová, M. Pometlová, R. Šlamberová., and Obsahuje bibliografii
Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic and worldwide. Previous studies have demonstrated the adverse effects of maternal drug abuse. However, the father's contribution as a parent and donor of the half genetic information is unclear. The present study aimed to examine the effect of paternal MA exposure on behavioral development and locomotor activity in rat offspring. MA was administrated subcutaneously for 30 days at a dose of 5 mg/kg to adult male rats. The impact of paternal MA exposure on rat pups was investigated using behavioral tests during development and locomotor activity tests in adulthood. Prior to testing, adult offspring were exposed to an acute challenge dose of MA (1 mg/kg) to examine the possible sensitizing effect of the paternal treatment. Our results found no significant differences in behavioral development or locomotor activity in adulthood of offspring linked to paternal MA application. These results differ from the effects induced by maternal MA application. Further, our results demonstrated a significant increase in locomotor activity on the Laboras test after acute MA application. When comparing sex differences, females showed more activity than males in adulthood, whereas males were more active during development.
Behavioral sensitization is defined as augmented psychomotor activity, which can be observed after drug re-administration following withdrawal of repeated drug exposure. It has been shown that abuse of one drug can lead to increased sensitivity to certain other drugs. This effect of developed general drug sensitivity is called cross-sensitization and has been reported between drugs with similar as well as different mechanisms of action. There is growing evidence that exposure to drugs in utero not only causes birth defects and delays in infant development, but also impairs the neural reward pathways, in the brains of developing offspring, in such a way that it can increase the tendency for drug addiction later in life. This review summarizes the results of preclinical studies that focused on testing
behavioral cross-sensitization, after prenatal methamphetamine exposure, to drugs administered in adulthood, with both similar and different mechanisms of action. Traditionally, behavioral sensitization has been examined using the Open field or the Laboras Test to record locomotor activity, and the Conditioned Place Preference and Self-administration test to examine drugseeking behavior. However, it seems that prenatal drug exposure can sensitize animals not only to the locomotor-stimulating and conditioning effects of drugs, but may also be responsible for modified responses to various drug effects.
Cíl. Cílem práce je posoudit dopad intenzivního užívání drog v dospívání na životní situaci dotázaných v době mladé dospělosti. Metody. V práci jsou využita data získaná při prvním vyšetření (1996 až 1998) a data z následného vyšetření (2010 až 2011). Informace vycházejí z řízených rozhovorů a dotazníků zaměřených na chování ve vztahu k návykovým látkám, osobnostní charakteristiky, sebehodnocení, duševní zdraví a životní spokojenost. Soubor tvoří 124 osob vyšetřených v době dospívání. Následné vyšetření s odstupem 14 let bylo realizováno u 52 osob (42 % původního souboru). Výsledky. Tři čtvrtiny osob z následného vyšetření bylo bez problémů s drogami. Problémová skupina oproti neproblémové častěji užívala v dospívání heroin a častěji ho užívala denně, měla více detoxifikací a více léčeb. Problémová skupina měla nižší životní spokojenost, ale v ostatních psychologických charakteristikách se od neproblémové skupiny nelišila. Závěry. Intenzivní užívání tvrdých drog v dospívání přetrvává do dospělosti u čtvrtiny souboru. Tři čtvrtiny sledovaných osob jsou sociálně adaptované, dlouhodobě stabilizované bez užívání drog. Adolescentní užívání drog má nepříznivý dopad na úroveň dosaženého vzdělání a zhoršuje možnosti pracovního uplatnění., b1_Objectives. The major goal of the study was to assess the impact of intensive drug use in adolescence in the life situation of the respondents at the period of young adulthood. Sample and setting. The analyses are based on data collected during the first examination (1996 to 1998) and during the reassessment in 2010/2011. Information was obtained through structured interviews and questionnaires focused on addictive behaviour, personality characteristics, self-esteem, mental health and life satisfaction. The sample consisted of 124 persons examined at the time of adolescence. The follow-up was carried out after 14 years with 52 persons (42% of original sample). Statistical analyses. T-test or nonparametric Mann-Whitney’s U test was applied to test differences in group means, χ2 test was used to explore differences in frequencies, and to test associations between variables the Pearson’s correlation coefficient was chosen. Results. Three quarters of the sample interviewed at the time of young adulthood were without drug problems. Subjects in the problem group compared to non-problem group more often used heroin in adolescence, more often used heroin on daily basis, and had more detoxifications and more drug treatments. Problem group had lower life satisfaction, but in other psychological characteristics did not differ from the non-problem group. Conclusions and limitations of the study. Intensive use of hard drugs in adolescence persisted into young adulthood in a quarter of the sample. Three quarters of the followed individuals are socially adapted and stabilized without drug use. Adolescent drug use has a detrimental effect on educational attainment and worse career prospects., b2_Two limitations of the study should be mentioned: the first is the low response rate at the follow-up; the second concerns the study site, which was limited to Prague, so the conclusions may be relevant to metropolitan population only., Ladislav Csémy [et al.]., and Obsahuje seznam literatury
The hyperpolarization-activated cyclic-nucleotide-gated
non-selective cation (HCN) channels play a potential role in the
neurological basis underlying drug addiction. However, little is
known about the role of HCN channels in methamphetamine
(METH) abuse. In the present study, we examined the changes
in working memory functions of METH re-exposed mice through
Morris water maze test, and investigated the protein expression
of HCN1 channels and potential mechanisms underlying the
modulation of HCN channels by Western blotting analysis. Mice
were injected with METH (1 mg/kg, i.p.) once per day for
6 consecutive days. After 5 days without METH, mice were
re-exposed to METH at the same concentration. We found that
METH re-exposure caused an enhancement of working memory,
and a decrease in the HCN1 channels protein expression in both
hippocampus and prefrontal cortex. The phosphorylated
extracellular regulated protein kinase 1/2 (p-ERK1/2),
an important regulator of HCN channels, was also obviously
reduced in hippocampus and prefrontal cortex of mice with METH
re-exposure. Meanwhile, acute METH exposure did not affect the
working memory function and the protein expressions of HCN1
channels and p-ERK1/2. Overall, our data firstly showed the
aberrant protein expression of HCN1 channels in METH
re-exposed mice with enhanced working memory, which was
probably related to the down-regulation of p-ERK1/2 protein
expression.
The aim of this study was to inve stigate the effect of prenatal methamphetamine (MA) exposure and application of the same drug in adulthood on cognitive functions of adult female rats. Animals were prenatally exposed to MA (5 mg/kg) or saline (control group). The cognitive function was tested as ability of spatial learning in the Morris Water Maze (MWM). Each day of the experiment animals received an injection of MA (1 mg/kg) or saline. Our results demonstrated that prenatal MA exposure did not affect the latency to reach the hidden platform or the distance traveled during the Place Navigation Test; however, the speed of swimming was increased in prenatally MA-exposed rats compared to controls regardless of the treatment in adulthood. MA treatment in adulthood increased the latency and distance when compared to controls regardless of the prenatal exposure. Neither prenatal exposure, nor tr eatment in adulthood affected memory retrieval. As far as the estrous cycle is concerned, our results showed that prenatally MA-exposed females in proestrus/estrus swam faster than females in diestrus. This effect of estrous cycle was not apparent in control females. In conclusion, our results indicate that postnatal, but not prenatal exposure to MA affects learning of adult female rats., E. Macúchová, K. Nohejlová-Deykun, R. Šlamberová., and Obsahuje bibliografii a bibliografické odkazy
Methamphetamine (MA) is an addictive psychostimulant with significant potential for abuse. Previous rat studies have demonstrated that MA use during pregnancy impairs maternal behavior and induced delayed development of affected pups. The
offspring of drug-addictive mothers were often neglected and exposed to neonatal stressors. The present study therefore examines the effect of perinatal stressors combined with exposure to prenatal MA on the development of pups and maternal behavior. Dams were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg). Litters were divided into four groups according to postnatal stressors: controls (N); maternal separation (S); maternal cold-water stress (W); maternal separation plus cold-water stress (SW). The pup-retrieval test showed differences among postnatally stressed mothers and non-stressed controls. The righting reflex on
a surface revealed delayed development of pups prenatally exposed to MA/SA and postnatal stress. Negative geotaxis and Rotarod results confirmed that the MA group was the most affected. Overall, our data suggests that a combination of perinatal stress and prenatal MA can have a detrimental effect on maternal behavior as well as on the sensorimotor development of pups. However, MA exposure during pregnancy seems to be the decisive factor for impairment.
It is known that psychostimulants including methamphetamine (MA) have neurotoxic effect, especially, if they are targeting CNS during its critical periods of development. The present study was aimed on evaluation of cognitive changes following scheduled prenatal MA exposure in combination with long-term exposure in adulthood of male rats. Two periods of gestation were targeted: 1st half - the embryonic day (ED) 1-11 and 2nd half - ED 12-22. Rat mothers received subcutaneously a daily injection of MA (5 mg/kg) or saline (SAL, 1 ml/kg) throughout scheduled periods. Male offspring were tested for cognitive changes in the Morris Water Maze (MWM) in adulthood. Each day of the experiment animals received an injection of MA (1 mg/kg) or SAL (1 ml/kg) during 12 days. Our results demonstrated that in the group of animals exposed to the drug during ED 1-11, neither prenatal MA exposure, nor adult MA treatment changed the performance in the MWM test. Only the velocity was increased in group with long-term MA treatment (SAL/MA and MA/MA). In the group of animals exposed to the drug during ED 12-22, rats exposed to MA prenatally and also in adulthood (MA/MA) swam faster but learned the position of the platform slower in the Place Navigation Test than animals exposed to SAL in adulthood (MA/SAL). In the Probe Test, MA/SAL had decreased velocity and swam shorter distance than MA/MA or SAL/SAL rats suggesting increased floating of these animals. In the Memory Retention Test, SAL/MA rats swam shorter distance than SAL/SAL or MA/MA animals suggesting changes in used strategies in memory recall. As conclusion, our results suggest differences in the effect of combination of prenatal and adult exposure to MA. These effects further depend on the stage of CNS development and schedule of MA exposure affecting intrauterine development in male rats., I. Hrebíčková, M. Malinová-Ševčíková, E. Macúchová, K. Nohejlová, R. Šlamberová., and Obsahuje bibliografii