The formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. Moreover, chemogenetic analysis revealed central amygdala as critical for linking appetitive emotional states with spatial contexts. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.
- MeSH
- amfetamin farmakologie MeSH
- amygdala fyziologie MeSH
- hipokampus * fyziologie MeSH
- konsolidace paměti * fyziologie MeSH
- krysa rodu rattus MeSH
- mozek fyziologie MeSH
- neurony fyziologie metabolismus MeSH
- nucleus accumbens * fyziologie MeSH
- odměna * MeSH
- paměť fyziologie MeSH
- podněty MeSH
- prefrontální mozková kůra fyziologie MeSH
- rozpomínání * fyziologie MeSH
- strojové učení MeSH
- tegmentum mesencephali - area ventralis * fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
This report presents a fatal case of a young female Type I diabetic patient who developed convulsions and loss of consciousness after taking methamphetamine and spending some time in a dance club. During the convulsions, she was given sugar and when no response occurred, her boyfriend who was not experienced in the use of insulin administered a dose of insulin to her. The woman lost consciousness and died despite the efforts of the emergency service. A biochemical analysis revealed a high level of insulin (196.67 mU/L) and low levels of glucose (2.96 mmol/L) and C-peptide (26 pmol/L). Toxicological analysis revealed a methamphetamine concentration of 389 ng/mL and an amphetamine concentration of 19 ng/mL. The forensic perspective of the difficult determination of the contribution of each of the factors to the death, i.e., the pre-existing medical condition (Type I diabetes), the use of methamphetamine, the physical exertion at the dance club, and, finally, the non-indicated administration of insulin, is discussed. The ruling of the court is also reported.
- MeSH
- bezvědomí chemicky indukované MeSH
- C-peptid krev MeSH
- diabetes mellitus 1. typu * MeSH
- dospělí MeSH
- fatální výsledek MeSH
- hypoglykemika škodlivé účinky MeSH
- inzulin * aplikace a dávkování MeSH
- krevní glukóza analýza MeSH
- lidé MeSH
- methamfetamin * škodlivé účinky MeSH
- poruchy spojené s užíváním amfetaminu komplikace MeSH
- stimulanty centrálního nervového systému * škodlivé účinky MeSH
- tanec MeSH
- tělesná námaha MeSH
- záchvaty MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® ChiraldexTM G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a LipodexTM D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-β-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the ChiraldexTM G-PN column. Six baseline and nine partial separations were observed with the LipodexTM D column, respectively.
- Klíčová slova
- Adipex retard,
- MeSH
- fentermin * dějiny MeSH
- lékové předpisy normy MeSH
- lidé MeSH
- psychotropní léky škodlivé účinky MeSH
- schvalování léčiv * zákonodárství a právo MeSH
- Check Tag
- lidé MeSH
Chuť i míra hladu, ale i rychlost metabolizmu jsou geneticky determinovány a regulace probíhá na třech úrovních v mozku a také ve střevě, a to pomocí střevních hormonů a neuromodulátorů. Hubnutí není fyziologický proces, tělo je nastaveno tak, že bychom měli neustále přibírat až na hmotnost, která je nám zřejmě geneticky předurčena. Poslední roky se objevují nové moderní a velmi bezpečné léky na hubnutí a na léčbu obezity jako nemoci. Začíná převládat názor, že obezitu je třeba léčit doživotně, za pomoci nejen změny životního stylu, ale také za použití léků nebo postupů bariatrické chirurgie.
Appetite and hunger, as well as metabolic rate, are genetically determined and regulated at three levels in the brain and also in the bowel by bowel hormones and neuromodulators. Weight loss is not a physiological process, the body is set up to enable continuous weigh gaining up to the weight that is probably genetically predetermined for us. In recent years, new modern and very safe drugs are emerging for weight loss and for treating obesity as a disease. The opinion that obesity should be treated for life, not only with lifestyle changes but also with drugs or bariatric surgery procedures, is becoming predominant.
- MeSH
- bupropion terapeutické užití MeSH
- fentermin terapeutické užití MeSH
- glukagonu podobný peptid 1 terapeutické užití MeSH
- látky proti obezitě aplikace a dávkování terapeutické užití MeSH
- liraglutid terapeutické užití MeSH
- nadváha etiologie farmakoterapie genetika psychologie terapie MeSH
- naltrexon terapeutické užití MeSH
- obezita etiologie farmakoterapie genetika psychologie terapie MeSH
- orlistat terapeutické užití MeSH
Neurotrophins are proteins included in development and functioning of various processed in mammalian organisms. They are important in early development but as well as during adulthood. Brain - derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been previously linked with many psychiatric disorders such as depression and addiction. Since during postnatal development, brain undergoes various functional and anatomical changes, we included preweaning environment enrichment (EE), since enrichment has been linked with improved function and development of the several brain structure such as hippocampus (HP), in which we monitored these changes. On the other hand, social isolation has been linked with depression and anxiety-like behavior, therefore postweaning social isolation has been added to this model as well and animal were exposed to this condition till adolescence. We examined if all these three factors had impact on BDNF and NGF levels during three phases of adolescence - postnatal days (PDs) 28, 35 and 45. Our results show that EE did not increase BDNF levels neither in control or MA exposed animals and these results are similar for both direct and indirect exposure. On the other side, social separation after weaning did reduce BDNF levels in comparison to standard housing animals but this effect was reversed by direct MA exposure. In terms of NGF, EE environment increased its levels only in indirectly exposed controls and MA animals during late adolescence. On the other hand, social separation increased NGF levels in majority of animals.
- MeSH
- hipokampus MeSH
- krysa rodu rattus MeSH
- methamfetamin * farmakologie MeSH
- mozek metabolismus MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- nervový růstový faktor metabolismus MeSH
- zpožděný efekt prenatální expozice * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Drug addiction and its effect on the behavior and development of children has become a serious problem in our society. Methamphetamine (MA) is one of the most abused psychostimulants in the Czech Republic, and its abuse is rising worldwide. Previous studies have demonstrated the adverse long-term effects of maternal drug abuse on rat offspring. However, the father's contribution as a parent and donor of half of the genetic information is unclear. Previous studies of other psychostimulant drugs indicate that long-term application of MA to adult male rats may induce changes in their reproductive system and lead to changes in rat pup functional and behavioral development. Therefore, the present review aimed to investigate the effect of MA administration on reproductive toxicity and sexual behavior of adult male rats, as well as the impact of paternal MA exposure on behavioral development and locomotor activity in rat offspring.
- MeSH
- chování zvířat MeSH
- dítě MeSH
- dospělí MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- methamfetamin * škodlivé účinky MeSH
- pohlavní orgány MeSH
- potkani Wistar MeSH
- sexuální chování MeSH
- stimulanty centrálního nervového systému * farmakologie MeSH
- zpožděný efekt prenatální expozice * chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
RATIONALE: Exposure to rewards can alter behavioral reactivity to them. For example, stimulants sensitize locomotor activation, whereas sexual experience sensitizes copulatory behaviors. Moreover, rewards can cross-sensitize one another. Although stimulants are known to cross-sensitize locomotor effects, the evidence for cross-sensitization between stimulants and sex is less clear. OBJECTIVES: This study determined the effects of single and repeated pre-exposure to methylphenidate (MPH) or sex on one another in adult male rats. METHODS: Cross-sensitization between MPH (5 mg/kg) and sex (30 min with sexually experienced female) was examined. Adult male rats were pre-exposed to 0, 1, or 10 trials of either sex or MPH before being exposed to the other reward. Locomotor chambers were used in MPH trials. Bilevel chambers were used in sexual trials, and sexual behaviors were video scored. RESULTS: The amount of prior sexual experience differentially influenced the ceiling of MPH-dependent sensitization; in the last drug trial, locomotion was highest in males given 1 previous sexual trial compared with 0 or 10. Compared with MPH-naive males, pre-exposure to MPH (1 and 10 trials) reduced the number of ejaculations without impacting sexual performance (intromission/mount latency and frequency). CONCLUSIONS: These findings indicate that the degree of pre-exposure to a reward can differentially affect reactivity to novel rewards. The results showed that previous findings of cross-sensitization between amphetamine and sex do not extend to MPH. However, exposure to MPH prior to sexual experience can increase the amount of sexual stimulation needed to achieve ejaculation.
- MeSH
- amfetamin farmakologie MeSH
- kopulace MeSH
- krysa rodu rattus MeSH
- methylfenidát * farmakologie MeSH
- stimulanty centrálního nervového systému * farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: There is a lack of studies on methamphetamine (MA) exposure and morbidity in children beyond the perinatal period. OBJECTIVES: We compared morbidity in children (0-3 years) with prenatal MA exposure to opioid-exposed and to non-exposed children. METHODS: We used data from a Czech nationwide, registry-based cohort study (2000-2014). Children, who reached 3 years of age, of mothers hospitalized with (i) MA use disorder during pregnancy (MA; n = 194), (ii) opioid use disorder during pregnancy (opioids; n = 166), and (iii) general population (GP; n = 1,294,349) with no recorded history of substance use disorder (SUD). Information on inpatient contacts, length of stay, and diagnoses (International Statistical Classification of Diseases and Related Health Problems 10th Revision [ICD-10]) were assessed. Crude and adjusted odds ratios (aOR), 95% confidence interval (CI) for the risk of hospitalization, and for getting diagnosis from the ICD-10 diagnosis chapters were calculated using binary logistic regression. A stratified analysis on hospitalizations with SUD of mothers was performed. RESULTS: No significant differences were found in the measures of hospitalization between the MA and opioid groups. Children prenatally exposed to MA and opioids had higher numbers of hospitalizations and diagnoses and longer stays in hospital than children in the GP. Increased risks of certain infectious and parasitic diseases were found in both MA (aOR = 1.6; CI: 1.1-2.3) and opioid (aOR = 1.9; 1.3-2.8) groups as compared to the GP group. The most pronounced difference in stratified analysis on maternal hospitalizations related to SUD after birth was observed for injury, poisoning, and certain other consequences of external causes in the strata of the MA group who had hospitalized mothers (aOR 6.3, 1.6-24.6) compared to the strata without maternal hospitalizations (aOR 1.4, 0.9-2.3). CONCLUSION: This study suggests that children born to mothers using MA during pregnancy have similar morbidity during the first 3 years of life but higher than the GP. The excess of risk was primarily due to infections and injuries in the MA group.
- MeSH
- dítě MeSH
- kohortové studie MeSH
- lidé MeSH
- methamfetamin * škodlivé účinky MeSH
- morbidita MeSH
- opioidní analgetika terapeutické užití MeSH
- poruchy spojené s užíváním opiátů * epidemiologie farmakoterapie MeSH
- registrace MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice * epidemiologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Tacrine was withdrawn from clinical use as a drug against Alzheimer's disease in 2013, mainly due to drug-induced liver injury. The culprit of tacrine-associated hepatotoxicity is believed to be the 7-OH-tacrine metabolite, a possible precursor of quinone methide (Qmeth), which binds to intracellular -SH proteins. In our study, several different animal and human models (liver microsomes, primary hepatocytes, and liver slices) were used to investigate the biotransformation and hepatotoxicity of tacrine and its 7-substituted analogues (7-methoxy-, 7-phenoxy-, and 7-OH-tacrine). Our goal was to find the most appropriate in vitro model for studying tacrine hepatotoxicity and, through rational structure modifications, to develop derivatives of tacrine that are less prone to Qmeth formation. Our results show that none of animal models tested accurately mimic human tacrine biotransformation; however, the murine model seems to be more suitable than the rat model. Tacrine metabolism was overall most accurately mimicked in three-dimensional (3D) spheroid cultures of primary human hepatocytes (PHHs). In this system, tacrine and 7-methoxytacrine were hydroxylated to 7-OH-tacrine, whereas 7-phenoxytacrine formed, as expected, only trace amounts. Surprisingly, however, our study showed that 7-OH-tacrine was the least hepatotoxic (7-OH-tacrine < tacrine < 7-methoxytacrine < 7-phenoxytacrine) even after doses had been adjusted to achieve the same intracellular concentrations. The formation of Qmeth-cysteine and Qmeth-glutathione adducts after human liver microsome incubation was confirmed by all of the studied tacrine derivatives, but these findings were not confirmed after incubation with 3D PHH spheroids. Therefore, the presented data call into question the suggested previously hypothesized mechanism of toxicity, and the results open new avenues for chemical modifications to improve the safety of novel tacrine derivatives.
- MeSH
- biotransformace MeSH
- indolochinony * MeSH
- krysa rodu rattus MeSH
- lékové postižení jater * MeSH
- lidé MeSH
- methamfetamin * MeSH
- myši MeSH
- takrin toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
