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.

• Klíčová slova
• Sprague-Dawley rats, depression, methamphetamine, olfactory bulbectomy, reinstatement, self-administration,
• 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
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

Regeneration of olfactory receptor neurones after bulbectomy can lead to formation of extrabulbar synapses, the functional significance of which remains controversial. Adult hooded rats (n = 27) were bilaterally bulbectomized under pentobarbital anaesthesia. Small pieces of brain tissues (1-2 mm3; OB: olfactory bulb; St: corpus striatum) were obtained from embryos of the same strain and placed into the bulbectomy-produced cavity in contact with the exposed brain surface. Smell was tested at 2- to 3-week intervals from 7 weeks to 7 months after the operation. The latency to find hidden food gradually improved and attained the intact control level in bulbectomized rats without grafts, but remained poor in the OB and St transplanted groups. Seven to ten months after transplantation, spontaneous unit activity and unit reactions to amyl acetate vapours were examined with a carbon fibre microelectrode. Unit responses in the transplants resembled those in the normal OB, but were less pronounced. Morphological examination of the transplant and of its connections with the olfactory receptor neurones and with the host brain suggested that functional recovery was mediated by the connections of the olfactory axons with the remnants of the OB, with the anterior olfactory nucleus and/or with the frontal cortex. The adverse effect of OB and St transplants was probably due to their poor connectivity with the host brain which prevented the regenerating olfactory axons from reaching higher olfactory centres.

• MeSH
• analýza rozptylu MeSH
• bulbus olfactorius anatomie a histologie   fyziologie   chirurgie   transplantace   MeSH
• čich MeSH
• corpus striatum transplantace   MeSH
• elektrofyziologie MeSH
• krysa rodu Rattus MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Regeneration of olfactory axons after bilateral bulbectomy in adult rats leads to atypical localization of the newly formed glomeruli. These structures are localized in the remnants of the olfactory bulb either in the previously deafferented glomerular layer or between external plexiform and granule cell layers in the close vicinity of mitral cells.

• MeSH
• bulbus olfactorius cytologie   fyziologie   MeSH
• hematoxylin MeSH
• krysa rodu Rattus MeSH
• regenerace nervu * MeSH
• železo MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• hematoxylin MeSH
• železo 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 účinky léků   metabolismus   patologie   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
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antidepresiva MeSH
• antioxidancia MeSH
• Casp3 protein, rat MeSH Prohlížeč
• glutathion MeSH
• glutathionperoxidasa MeSH
• kaspasa 3 MeSH
• L-laktátdehydrogenasa MeSH
• melatonin MeSH
• superoxiddismutasa MeSH

One of the major neuropeptide groups in insects is adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides. AKH had improving effects on depression and anxiety in animal models and it may be a new treatment choice in these disorders. Aim of this study was to investigate effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH) and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on animal behavior in olfactory bulbectomy (OBX) model and in posttraumatic stress disorder (PTSD) model of Wistar-albino rats. Lia-AKH and Pht-HrTH significantly increased time spent in escape platform's quadrant compared to sham control while Lia-AKH significantly increased time spent in escape platform's quadrant compared to OBX controls in probe trial of Morris water maze (MWM). Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased immobility time compared to OBX controls in forced swimming test (FST). Pht-HrTH significantly increased %open arm time compared to OBX controls in elevated plus maze (EPM) test. Ani-AKH significantly increased %open arm entry compared to sham control while Ani-AKH and Pht-HrTH significantly increased %open arm entry compared to OBX controls in EPM. In PTSD study Ani-AKH and Lia-AKH significantly decreased immobility time compared to traumatized controls in FST. In acoustic startle reflex test, Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased average startle amplitude compared to non-traumatized controls in PTSD study. Metabolomic studies showed that AKH may affect glutamatergic and dopaminergic system and neurochemistry. In conclusion, AKH peptides had wide ranging effects on behavior and improved performance in OBX and PTSD models in rats.

• Klíčová slova
• Adipokinetic hormone, Animal model, Behavior, Neurochemistry, Olfactory bulbectomy, PTSD,
• MeSH
• bulbus olfactorius chirurgie   MeSH
• chování zvířat MeSH
• hmyzí hormony farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• neuropeptidy farmakologie   MeSH
• oligopeptidy farmakologie   MeSH
• posttraumatická stresová porucha farmakoterapie   metabolismus   patologie   MeSH
• potkani Wistar MeSH
• úzkost farmakoterapie   metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adipokinetic hormone MeSH Prohlížeč
• hmyzí hormony MeSH
• kyselina pyrrolidonkarboxylová MeSH
• neuropeptidy MeSH
• oligopeptidy MeSH
• red pigment-concentrating hormone MeSH Prohlížeč

Depression is a psychiatric disorder characterized by a marked decrease in reward sensitivity. By using the olfactory bulbectomy (OBX) model of depression, it was shown that OBX rats display enhanced drug-taking and seeking behaviors in a self-administration paradigm than sham-operated (SHAM) controls, and sex is an important regulating factor. To reveal potential strain effects, we compared the operant behavior of male and female Sprague-Dawley and Wistar OBX and SHAM rats trained to self-administer palatable food pellets. Results showed that Sprague-Dawley OBX rats of both sexes exhibited lower operant responding rates and food intake than SHAM controls. Food restriction increased responding in both OBX and SHAM groups. Female rats responded more than males, but the OBX lesion abolished this effect. In Wistar rats, bulbectomy lowered food self-administration only during the last training days. Food self-administration was not significantly affected in Wistar rats by sex. In summary, this study showed that bulbectomy significantly reduces operant responding and food intake in male and female Sprague-Dawley rats while inducing a mild reducing effect only in the Wistar strain. Strain-dependent effects were also observed in the modulating role of sex and food restriction on operant responding and palatable food intake.

• Klíčová slova
• depression, olfactory bulbectomy, reward, self-administration, sex, strain,
• Publikační typ
• časopisecké články MeSH

In the present study we investigated the effect of a two-stage bilateral lesion of the olfactory bulb (OB) in rats on the regeneration ability of peripheral olfactory neurons and their reinnervation capacity in the spared OB. The outgrowth of newly-generated olfactory axons as well as the maturation of their terminal synaptic field was detected by immunohistochemistry of the growth-associated phosphoprotein B-50/GAP-43. In addition, the glial response to the surgery was monitored by an immunohistochemical marker for astrocytes, glial fibrillary acidic protein (GFAP). In neonatal rats (P3-P5), the right OB was removed, then three months later the contralateral side was ablated. Six days after the second operation the animals were transcardially perfused. Their brains were embedded in paraplast, serially sectioned and processed for histological and immunohistochemical observations. After neonatal OB ablation, homogeneous B-50-immunoreactivity (BIR) was found in the forebrain, olfactory axons and ectopic glomeruli localized in the small OB remnant-like structures and in the regenerated neuroepithelium. A strong GFAP response was revealed in the brain cortex as well as in the newly-formed olfactory axons and glomeruli-like structures of the OB remnants. After adult OB ablation strong BIR was observed in olfactory axons, while remaining glomerular structures were only faintly stained. The neuroepithelium revealed signs of massive degenerative processes with a substantial decrease in BIR. The GFAP-positive astrocytes were scattered throughout the entire OB remnant and were prominent in the glomeruli-like structures and adjacent frontal cortex. In the present study, we applied GAP-43 and GFAP immunohistochemistry to characterize the responses of individual olfactory components after two-stage olfactory bulbectomy. Furthermore, this model of OB ablation characterized by two immunohistochemical markers could elucidate certain molecular mechanisms involved in the regeneration and/or plasticity of the olfactory system.

• MeSH
• bulbus olfactorius metabolismus   patologie   fyziologie   MeSH
• gliový fibrilární kyselý protein metabolismus   MeSH
• imunohistochemie MeSH
• krysa rodu Rattus MeSH
• neurony metabolismus   patologie   fyziologie   MeSH
• potkani Wistar MeSH
• protein GAP-43 metabolismus   MeSH
• regenerace nervu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• gliový fibrilární kyselý protein MeSH
• protein GAP-43 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
• Názvy látek
• methamfetamin 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
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH

BACKGROUND: Neurotrophins, especially brain-derived neurotrophic factor (BDNF) have gained significant therapeutic interest particularly in neurologic and psychiatric disorders and they have been found in human breast milk of mothers who suffered from adverse outcomes in pregnancy. This study tested the hypothesis that oral administration of BDNF/GDNF (glial cell line-derived neurotrophic factor) can exert a biological effect in a rat model of severe neuropathology induced by olfactory bulbectomy (OBX), which exhibits dysregulation of BDNF signaling and impaired blood-brain barrier. METHODS: Adult male albino Sprague-Dawley rats underwent the OBX surgery and separate groups of OBX and sham-operated controls received one oral dose of vehicle, BDNF (0.005 mg/kg), GDNF (0.03 mg/kg) or their combination. One week after neurotrophin dosing the rats were sacrificed and BDNF level was assessed by ELISA in the blood serum and cerebrospinal fluid. RESULTS: A significant decrease of serum BDNF level was found in the OBX model. This alteration was normalized by all types of treatment BDNF, GDNF, or their combination. No influence of sham surgery or treatment was observed in the control rats. BDNF levels in cerebrospinal fluid were below detection limit. CONCLUSION: This study indicates that oral administration of neurotrophins is able to exert a biological effect in the OBX model. There is a number of potential mechanisms, which remain to be elucidated.

• Klíčová slova
• BDNF, GDNF, Neurotrophins, Olfactory bulbectomy, Rats,
• MeSH
• aplikace orální MeSH
• biologický transport MeSH
• bulbus olfactorius chirurgie   MeSH
• hematoencefalická bariéra účinky léků   metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• mozkový neurotrofický faktor aplikace a dávkování   krev   mozkomíšní mok   MeSH
• nemoci mozku krev   MeSH
• neurotrofní faktory aplikace a dávkování   krev   mozkomíšní mok   MeSH
• ověření koncepční studie MeSH
• potkani Sprague-Dawley MeSH
• rekombinantní proteiny MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BDNF protein, human MeSH Prohlížeč
• CDNF protein, human MeSH Prohlížeč
• mozkový neurotrofický faktor MeSH
• neurotrofní faktory MeSH
• rekombinantní proteiny MeSH