Bulbectomy Dotaz Zobrazit nápovědu
- MeSH
- bulbus olfactorius chirurgie MeSH
- elektrofyziologie metody MeSH
- embryonální struktury transplantace MeSH
- histologické techniky metody MeSH
- krysa rodu rattus MeSH
- mozek MeSH
- pátrací chování fyziologie MeSH
- transplantace mozkové tkáně MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- bulbus olfactorius MeSH
- krysa rodu rattus MeSH
- poruchy paměti MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
In this study we analyzed the effects of melatonin (Mel, 1 mg/kg ip) on behavioral changes as well as cell and oxidative damage prompted by bilaterally olfactory bulbectomy. Olfactory bulbectomy caused an increase in lipid peroxidation products and caspase-3, whereas it prompted a decrease of reduced glutathione (GSH) content and antioxidative enzymes activities. Additionally, olfactory bulbectomy induced behavioral changes characterized by the enhancement of immobility time in the forced swim test and hyperactivity in the open field test. All these changes were normalized by treatment of Mel (14 days). Our data show that Mel has a beneficial neuropsychiatric action against oxidative stress, cell damage and behavior alterations.
- MeSH
- antidepresiva aplikace a dávkování farmakologie MeSH
- antioxidancia aplikace a dávkování farmakologie MeSH
- apoptóza účinky léků MeSH
- bulbus olfactorius chirurgie MeSH
- chování zvířat účinky léků MeSH
- glutathion metabolismus MeSH
- glutathionperoxidasa metabolismus MeSH
- injekce intraperitoneální MeSH
- kaspasa 3 metabolismus MeSH
- krysa rodu rattus MeSH
- L-laktátdehydrogenasa metabolismus MeSH
- melatonin aplikace a dávkování farmakologie MeSH
- mozek metabolismus patologie účinky léků MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- plavání MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- superoxiddismutasa metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Drug addiction is commonly associated with depression and comorbid patients also suffer from higher cravings and increased relapse rate. To address this issue preclinically we combined the olfactory bulbectomy (OBX) model of depression and intravenous methamphetamine self-administration procedure in rats to assess differences in relapse-like behavior. Male Sprague-Dawley rats were divided randomly into two groups; in one group the bilateral olfactory bulbectomy (OBX) was performed while the other group was sham operated. After recovery, intracardiac catheter was implanted. Intravenous self-administration procedure was conducted in operant boxes using nose-poke operandi (Coulbourn Instruments, Inc., USA) under fixed ratio 1 schedule of reinforcement. Methamphetamine was available at dose 0.08 mg/kg/infusion. After stable methamphetamine intake was maintained, a period of forced abstinence was initiated and rats were kept in their home-cages for 14 days. Finally, one reinstatement session was conducted in operant boxes with no drug delivery. In the reinstatement session the mean of 138.4 active nose-pokes was performed by the OBX group, while the sham group displayed 41 responses, i.e. 140 % and 48 % of basal nose-poking during maintenance phase in OBX and sham operated group respectively. OBX group also showed significantly more passive nose-pokes indicating hyperactive behavioral traits in bulbectomized rats. However, the % of active operandum preference was equal in both groups. Olfactory bulbectomy model significantly increased reinstatement of methamphetamine seeking behavior. This paradigm can be used to evaluate potential drugs that are able to suppress the drug-seeking behavior.
- MeSH
- autoaplikace MeSH
- bulbus olfactorius patofyziologie chirurgie MeSH
- chování při shánění drogy fyziologie MeSH
- depresivní poruchy komplikace patofyziologie MeSH
- intravenózní podání MeSH
- methamfetamin aplikace a dávkování MeSH
- modely nemocí na zvířatech MeSH
- náhodné rozdělení MeSH
- operantní podmiňování účinky léků fyziologie MeSH
- poruchy spojené s užíváním amfetaminu komplikace patofyziologie MeSH
- potkani Sprague-Dawley MeSH
- recidiva MeSH
- stimulanty centrálního nervového systému aplikace a dávkování MeSH
- zaváděcí katétry MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
Olfactory bulbectomy in rodents is considered a putative model of depression. Depression is often associated with drug addiction. Our previous studies demonstrated that methamphetamine (MA) administration to rat mothers affects both, mothers and their pups. The aim of the present study was to examine the effect of bulbectomy, as a model of depression, and MA administration on behavior of rat mothers and postnatal development of their pups. Adult female Wistar rats were randomly divided into two groups: bulbectomized (OBX) and sham-operated (SH). A period of 20 days was allowed for the development of the depressive-like phenotype. Animals were tested in the motor activity test and 2 % sucrose preference for anhedonia and hyperactive locomotor response to a novel environment, respectively. After then females were impregnated. Pregnant females were exposed to daily subcutaneous (s.c.) injection of MA (5 mg/kg) or saline (SA) during the entire gestation period. Postnatally, maternal behavior and pup development was examined. The effect of a challenge dose of MA (1 mg/kg, s.c.) on behavior was further examined in adult male offspring. Our results showed no differences in the maternal behavior as a matter of bulbectomy, only OBX rats slept more than all the SH controls. Pups from OBX mothers were born with lower birthweight and gained less weight during the postnatal development than pups from SH controls. Both, bulbectomy and MA administration, delayed the eyes opening. As a matter of functional development of the pups, maternal OBX procedure impaired the performance in the Bar-holding test, but only in saline group. OBX/SA group was the worst in the Bar-holding test relative to all the other groups. In addition, pups from OBX mothers dropped more boluses during the Bar-holding test, suggesting that they were more stressed. In adult male offspring, bulbectomy increased immobility only in the SA/SA group. Prenatal MA exposure increased locomotion, while decreasing immobility. In addition, challenge dose of MA in adulthood increased distance traveled, locomotion, rearing, and average and maximal velocity, while decreasing immobility and grooming. In conclusion, our results suggest that depressive-like phenotype of rat mothers induces impairment in somatic and functional development of their male offspring.
- MeSH
- bulbus olfactorius chirurgie MeSH
- krysa rodu rattus MeSH
- lokomoce MeSH
- methamfetamin toxicita MeSH
- náhodné rozdělení MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- stimulanty centrálního nervového systému toxicita MeSH
- těhotenství MeSH
- tělesná hmotnost účinky léků fyziologie 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
- MeSH
- čichové buňky * cytologie růst a vývoj zranění MeSH
- krysa rodu rattus * MeSH
- mozek MeSH
- regenerace fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus * MeSH
- zvířata MeSH
- Publikační typ
- abstrakty MeSH
Depression is frequently comorbid with a drug addiction and may seriously complicate its treatment. Currently, there is no routinely used animal model to investigate this comorbidity. In this study the effect of repeated administration of methamphetamine on i.v. drug self-administration in an olfactory bulbectomy model of depression in rats was investigated in order to propose and validate a rat model of comorbid depression and addiction. Male Wistar rats were either olfactory-bulbectomized (OBX) or sham-operated. They subsequently underwent a methamphetamine sensitization regime, which consisted of daily i.p. injections of methamphetamine for a 14-d period; controls received Sal injections at the same frequency. The i.v. self-administration of methamphetamine (0.08 mg/kg in one infusion) paradigm on a fixed ratio schedule of reinforcement was performed using operant chambers. A significant decrease of the drug intake was recorded in sham-operated animals pretreated with methamphetamine when compared to the unpretreated group. This was not apparent in the OBX groups. Both groups of OBX animals exhibited a higher intake of methamphetamine compared to the corresponding sham-operated groups, thus confirming the hypothesis of higher drug intake in depressive conditions in this rodent model. The procedure of behavioural sensitization to methamphetamine decreased the number of self-administered drug doses per session in the sham-operated rats. It is hypothesized that this phenomenon resulted from increasing efficacy of the drug after behavioural sensitization caused by repeated methamphetamine intermittent administration.
- MeSH
- autoaplikace MeSH
- bulbus olfactorius účinky léků chirurgie MeSH
- deprese farmakoterapie psychologie MeSH
- krysa rodu rattus MeSH
- methamfetamin aplikace a dávkování MeSH
- modely nemocí na zvířatech * MeSH
- návykové chování farmakoterapie prevence a kontrola psychologie MeSH
- potkani Wistar MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH