- Publikační typ
- abstrakt z konference MeSH
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.
- MeSH
- krysa rodu rattus MeSH
- maternální deprivace MeSH
- mateřské chování účinky léků fyziologie psychologie MeSH
- methamfetamin toxicita MeSH
- metoda rotující tyčky metody psychologie MeSH
- náhodné rozdělení MeSH
- novorozená zvířata MeSH
- poruchy spojené s užíváním psychoaktivních látek komplikace patofyziologie psychologie MeSH
- potkani Wistar MeSH
- psychický stres komplikace patofyziologie psychologie MeSH
- psychomotorický výkon účinky léků fyziologie MeSH
- stimulanty centrálního nervového systému toxicita MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice chemicky indukované patofyziologie psychologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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 drug-seeking 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.
- MeSH
- lidé MeSH
- lokomoce účinky léků fyziologie MeSH
- methamfetamin aplikace a dávkování škodlivé účinky MeSH
- modely u zvířat * MeSH
- poruchy spojené s užíváním psychoaktivních látek etiologie metabolismus psychologie MeSH
- stimulanty centrálního nervového systému aplikace a dávkování MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice chemicky indukované metabolismus psychologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Už několik let dominuje metamfetamin (MA) drogovému trhu jak v České republice, tak na Slovensku, avšak alarmující je i jeho spotřeba celosvětově. Stále rostoucí počet studií poukazuje na fakt, že vystavení MA in utero nezpůsobuje jenom vývojové vady a poruchy ve vývoji centrálního nervového systému, ale může vést k takovým změnám ve vyvíjejícím se systému odměny mozku, které zvýší pravděpodobnost k rozvoji drogové závislosti později v životě. Dostupné studie na animálních modelech poukazují na fakt, že potomci matek, kteří byli vystaveni prenatálně účinkům MA, jsou citlivější k aplikaci MA v dospělosti. Pro zvýšenou citlivost na účinky drogy byl zaveden termín senzitizace a ta je definována jako zvýšená psychomotorická aktivita po jednorázové aplikaci drogy, když dříve došlo k návyku na tuto drogu. Senzitizace byla pozorována nejen po opakovaném podávání drogy v dospělosti, ale také po chronické prenatální expozici účinkům drogy. Výsledky našich studií ukazují, že prenatální expozice MA zvyšuje citlivost k účinku aplikace drog v dospělosti, konkrétně k těm s podobným mechanismem účinku.
Women, who abuse drugs during pregnancy, expose not just themselves but also their developing fetus 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 behavior 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 sensitivity, the term of sensitization has been introduced. It is defined as augmented psychomotor activity, which can be observed after drug re-administration following discontinuation of repeated drug exposure, and has been demonstrated to develop not only after repeated drug administration in adulthood, but also after chronic prenatal exposure. Results from our studies have shown that prenatal MA exposure can influence the sensitivity to the effects of some drugs, given as a challenge, in adulthood, specifically to those with a similar action mechanism. Our findings indicate that cross-sensitization between prenatal MA exposure and adult drug treatment cannot be simply termed as a general drug addiction, since it seems that the mechanism by which a drug impairs specific neurotransmitter systems plays an important role. The study findings show that although the offspring of MA-addicted mothers have altered sensitivity to certain drugs in adulthood, they do not display increased active drug-seeking behavior. Therefore, if we extrapolate the results to humans, it appears that there is a relatively little risk that a person, whose mother abused MA during pregnancy, will actively seek out drugs.
- MeSH
- chování zvířat účinky léků MeSH
- dopamin metabolismus MeSH
- kanabinoidy farmakologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- matka - expozice noxám MeSH
- methamfetamin farmakologie MeSH
- modely nemocí na zvířatech MeSH
- návykové chování * chemicky indukované patofyziologie MeSH
- nucleus accumbens metabolismus MeSH
- opioidní analgetika farmakologie MeSH
- poruchy spojené s užíváním amfetaminu patofyziologie MeSH
- poruchy spojené s užíváním psychoaktivních látek * patofyziologie MeSH
- stimulanty centrálního nervového systému farmakologie MeSH
- tegmentum mesencephali - area ventralis metabolismus MeSH
- těhotenství účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- těhotenství účinky léků MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
The aim of the present study was to compare effect of three low doses of morphine (MOR) and delta9-tetrahydrocannabinol (THC) on social behavior tested in Social interaction test (SIT). 45 min prior to testing adult male rats received one of the drugs or solvents: MOR (1; 2.5; 5 mg/kg); saline as a solvent for MOR; THC (0.5; 1; 2 mg/kg); ethanol as a solvent for THC. Occurrence and time spent in specific patterns of social interactions (SI) and non-social activities (locomotion and rearing) was video-recorded for 5 min and then analyzed. MOR in doses of 1 and 2.5 mg/kg displayed decreased SI in total. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. The highest dose (5 mg/kg) of MOR decreased following and increased genital investigation. Rearing activity was increased by lower doses of MOR (1 and 2.5 mg/kg). THC, in each of the tested doses, did not induce any specific changes when compared to matching control group (ethanol). However, an additional statistical analysis showed differences between all THC groups and their ethanol control group when compared to saline controls. There was lower SI in total, lower mutual sniffing and allo-grooming, but higher rearing in THC and ethanol groups than in saline control group. Thus, changes seen in THC and ethanol groups are seemed to be attributed mainly to the effect of the ethanol. Based on the present results we can assume that opioids affect SI more than cannabinoid.
Different forms of anxiety-related behavior have been reported after a single drug use of many abused substances, however, less is known about how males and females are affected differently from exposure to various drugs. Furthermore, chronic prenatal methamphetamine (MA) exposure was shown to predispose the animal to an increased sensitivity to drugs administrated in adulthood. Using the Elevated plus-maze test (EPM), the first aim of the present study was to examine how male and female rats are affected by acute drug treatment with subcutaneously (s.c.) administrated (a) MA (1mg/kg); (b) drugs with a similar mechanism of action to MA: amphetamine (AMP, 1mg/kg), cocaine (COC, 5mg/kg), 3,4-methylenedioxymethamphetamine (MDMA, 5mg/kg); and (c) drugs with different mechanisms of action: morphine (MOR, 5mg/kg), and Δ 9-tetrahydrocannabinol (THC, 2mg/kg). The second aim was to determine if prenatally MA-exposed (5mg/kg) animals show an increased sensitivity to adult drug treatment. The parameters analyzed were divided into two categories: anxiety-related behavior and anxiety-unrelated/exploratory behavior. Our results showed in female rats a decreased percentage of the time spent in the closed arms (CA) after MA, and an increased percentage of the time spent in the open arms (OA) after MA, AMP, and COC treatment, indicating an anxiolytic-like effect. In females, MDMA and THC treatment increased the percentage of the time spent in the CA. An increased percentage of the time spent in the CA was also seen after MOR treatment in females as well as in males, indicating an anxiogenic-like effect. As far as the interaction between prenatal MA exposure and adult drug treatment is concerned, there was no effect found. In conclusion, it seems that: (a) in some cases female rats are more vulnerable to acute drug treatment, in terms of either anxiogenic- or anxiolytic-like effects; (b) prenatal MA exposure does not sensitize animals to the anxiety-related effects of any of the drugs.
- MeSH
- analgetika farmakologie MeSH
- analýza rozptylu MeSH
- bludiště - učení účinky léků MeSH
- časové faktory MeSH
- estrální cyklus účinky léků MeSH
- krysa rodu rattus MeSH
- methamfetamin toxicita MeSH
- N-methyl-3,4-methylendioxyamfetamin farmakologie MeSH
- pátrací chování účinky léků MeSH
- serotoninové látky farmakologie MeSH
- sexuální faktory MeSH
- stimulanty centrálního nervového systému toxicita MeSH
- těhotenství MeSH
- úzkost chemicky indukované MeSH
- zpožděný efekt prenatální expozice chemicky indukované patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
