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Determination of critical developmental periods for effects of methamphetamine on rat behavior in adulthood
Hrebíčková, Ivana ; Šlamberová, Romana (advisor) ; Cendelín, Jan (referee) ; Valeš, Karel (referee)
Aim: The aim of the Ph.D. thesis was to find out which of the neuro-ontogenetic stages of laboratory rat is more significant for the methamphetamine (MA) exposure on the behavior in adulthood and to determine a critical developmental period for the effects of this drug. In the experimental part of the study was to test the influence of prenatal and neonatal MA exposure on behavior, social interaction, cognition and drug-seeking behavior in adulthood. Methods: Adult female rats were exposed to MA (5 mg/ml/kg) or saline (S) (1 mg/kg) during different stages of gestation and lactation. The tested substances were administered subcutaneously during the first half of gestation (ED 1-11), the second half of gestation (ED 12-22) or during early lactation (PD 1-11). The effect of prenatal MA exposure was transmitted to pups via placental barrier; the effect of MA exposure during early lactation was transmitted via the breast milk. In order to compare the rate of drug transmission by indirect MA exposure via the breast milk, we chose another group of offspring that we administered the tested substances directly subcutaneously during the same application period (PD 1-11). In this way we obtained 8 groups of exposed pups: ED 1-11 MA, S; ED 12-22 MA, S; PD 1-11 indirectly MA, S; PD 1-11 directly MA, S. These...
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Does prenatal methamphetamine exposure induce cross-sensitisation to drugs in adult male and female rats?
Macúchová, Eva ; Šlamberová, Romana (advisor) ; Šulcová, Alexandra (referee) ; Valeš, Karel (referee)
Women, who abuse drugs during pregnancy, expose not just themselves but also their developing foetus to impairing effects, which can have potentially harmful and even long- term effects on the exposed children. For some years, methamphetamine (MA) has dominated the illicit drug market in the Czech Republic and Slovakia; additionally this drug is on the rise worldwide. It is one of the most accessible drugs, and in many cases the first choice drug for many drug-addicted pregnant women; in part due to its anorectic and stimulant effects. These women are rarely aware of the consequences of their behaviour and their pregnancy is hardly ever a good enough reason for giving up drug use. These findings are supported by many experimental studies that show the damaging effects of maternal MA exposure on their offspring. There is growing evidence that exposure to MA in utero not only causes birth defects and delays in infant development, but also impairs the brain reward neural pathways of a developing offspring in such a way, that it could increase the predisposition for drug addiction later in life. Previously published animal studies have shown that offspring of mothers exposed to MA during pregnancy are more sensitive to MA when they encounter this drug later in adulthood. With respect to increased...
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The effect of prenatal MA exposure and crossfostering on functional changes in laboratory rat
Hrubá, Lenka ; Šlamberová, Romana (advisor) ; Tejkalová, Hana Barbora (referee) ; Šulcová, Alexandra (referee)
The aim of our study was to investigate the impact of prenatal methamphetamine (MA) exposure and cross-fostering on development of rat pups during preweaning period and on behavior, anxiety, cognitive function and nociception in adulthood. Mothers were daily exposed to injection of MA (5 mg/kg) or saline (S) approximately for 9 weeks: three weeks prior to impregnation, throughout the entire gestation period and for 23 days of lactation. Control females (C) did not receive any injection. 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 two treatments. We obtained 9 experimental groups (C/C, C/S, C/MA, S/C, S/S, S/MA, MA/C, MA/S, MA/MA). Pups were tested during postnatal development by means of following behavioral tests: negative geotaxis, tail pull, righting reflex on surface and in mid-air, rotarod and bar-holding and were examined for physiological maturation. In adulthood, males and females rats were tested in the Open field (OF) and in the Elevated plus maze (EPM) for behavior and anxiety and in the Plantar test for thermal nociception. Adult male rats were tested on cognitive function in the Morris water maze (MWM). In adult female rats, phases of the estrous cycle were recognized and compared. Our...
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Drug sensitization in rats prenatally exposed to methamphetamine
Schutová, Barbora ; Šlamberová, Romana (advisor) ; Šulcová, Alexandra (referee) ; Kršiak, Miloslav (referee)
Methamphetamine (MA) is a psychostimulant drug with high potential for abuse. Psychostimulants were shown to cause behavioral sensitization - a progressive increase of their psychomotor activating effects. Since half of MA users are women of reproductive age, there is an increased risk of negative consequences for their children. The aim of my dissertation thesis was to find out whether prenatal MA exposure is able to increase sensitivity to the same drug in adulthood. Pregnant dams were injected daily with MA 5 mg/kg or saline (S) subcutaneously (s.c.) during the whole gestation. The absolute control group of adult females (C) was not exposed to any injection application. To test the sensitivity of the offspring to MA in adulthood, half of each prenatally exposed group (MA, S, C) were administered MA 1 mg/kg while the other half received S s.c. The sensitizing effect of prenatal MA exposure was tested in the open field, elevated plus maze, Laboras (Metris B.V., Netherlands), Morris water maze, tail-flick test and in the tests of susceptibility to epileptic seizures. Our results showed that the animals prenatally exposed to MA were more susceptible to flurothyl seizures and demonstrated better performance in the test of memory. On the other hand, acute MA application in adulthood increased motor activity,...
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Systemic Coapplication of α1- a β-adrenergic Antagonists and Their Effects on Rat Cognition
Prokopová, Iva ; Šlamberová, Romana (referee) ; Pávek, Petr (advisor)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Iva Prokopová Supervisors: RNDr. Aleš Stuchlík, PhD (FgÚ AV ČR, v.v.i.) Doc. PharmDr. Petr Pávek, PhD (FaF, UK) Title of rigorous thesis: Systemic coapplication of α1- a β-adrenergic antagonists and their effects on rat cognition Spatial learning is a widely-studied type of animal behavior, often considered as a model of human higher cognitive functions. Noradrenergic receptors play a modulatory role in vigilance, attention, reward, learning and memory. The present study aimed at studying the effects of separate or combined systemic administration of α1-adrenergic antagonist prazosin (1 and 2 mg/kg) and β-blocker propranolol (5 and 20 mg/kg) on hippocampus-dependent learning of the active allothetic place avoidance (AAPA) task. Both centrally-active drugs impaired spatial learning when administered together, exerting no effect after separate applications. Locomotion was impaired only by combined application of higher doses of both drugs (2 mg/kg prazosin and 20 mg/kg propranolol). These results suggest an in vivo interaction between these two types of receptors in regulation of spatial navigation. Since there are several combined adrenoceptor blockers (antagonizing both α-...
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The role of main excitatory and inhibitory transmitters in epileptic seizures and the effect of antiepileptic drugs in the immature brain
Liptáková, Soňa ; Mareš, Pavel (advisor) ; Komárek, Vladimír (referee) ; Šlamberová, Romana (referee)
Epilepsy affects 50 million people worldwide. Approximately 50% of epilepsies start in the infancy and childhood. In addition, there are several age-bound epileptic syndromes which are difficult to treat. Due to these facts, developmental studies of epileptic seizures are of primary importance. Predominance of excitation over inhibition is a mechanism of nearly all types of epileptic seizures. Hypothesis that this compromised balance can be normalized by drugs affecting main excitatory and inhibitory system at different stages of brain development was tested in models with different pathogenesis. Our studies demonstrated that seizures induced by derrangement of GABAergic inhibition can be suppressed by antagonists of NMDA receptors (MK-801) and vice versa seizures with glutamatergic pathogenesis can be affected by drugs potentiating GABAergic system (valproate, ganaxolone) at all developmental stages in immature rats. Analysis of site of action of NMDA receptor antagonists demonstrated reciprocal function of anterior and posterior parts of substantia nigra, structure important for spread of epileptic activity to spinal cord. Special attention was given to an age-dependent model - flexion, emprosthotonic seizures elicited by administration of NMDA. Valproic acid, which potentiates GABAergic inhibition,...
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