A comprehensive assessment of the cholinergic-supporting and cognitive-enhancing effects of Rosa damascena Mill. (Damask rose) essential oil on scopolamine-induced amnestic rats.

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues. METHODS: The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 µL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor. RESULTS: According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically -citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active-state human M1 mAChR and anchored here chiefly by hydrogen-bonding and alkyl-π interactions. CONCLUSION: Our findings offer a solid experimental foundation for future RDEO-based medicinal product development for patients suffering from AD.

Investigation of Brucella canis and Brucella abortus Seropositivity by In-House Rapid Slide Agglutination Test and In-House ELISA in Northern Cyprus.

The incidence of Brucella canis (B. canis) in humans is unknown in Northern Cyprus. In this study, we investigated the prevalence of B. canis and Brucella abortus (B. abortus) infection in human sera and evaluated the results obtained by agglutination-based techniques using standardized antigens made from B. canis comparatively. All of the subjects were negative in terms of Rose-Bengal plate test. Undiluted serum samples were initially screened by rapid slide agglutination test (RSAT), and those which were found positive were retested in the dilution of 1/25-1/200. Confirmation of the positive results was performed by using 2-mercaptoethanol standard agglutination test (SAT). The test antigen was prepared from the less mucoid M (-) variant of B. canis, and 1/1,048 titered dog antiserum was used as positive control. In 225 serum samples, 3.6% (8/225) was positive by B. canis M (-) RSAT, 4.4 % (10/225) was positive by B. canis M (-) indirect enzyme-linked immunosorbent assay (iELISA). 5.3% (12/225) was positive by B. abortus S99 RSAT and 9.8% (22/225) was positive by B. abortus S99 iELISA. Nine samples were positive by both B. abortus S99 RSAT and B. abortus S99 iELISA. Seven samples were positive by both B. canis M (-) RSAT and B. canis M (-) iELISA. One patient was positive by all methods. It is important to evaluate patient samples with RSAT and iELISA. Until the notification system gives better results to the Ministry of Health, in order to reach the real data for Northern Cyprus, multicenter prevalence determination studies should be done for future.

Frequency of Developing COVID-19 Pneumonia in Patients Who Were Vaccinated Double-Dose CoronaVac: Data of the Pandemic Authorized Hospital in Northern Cyprus.

Background: RT-PCR is the leading method used in the diagnosis of COVID-19, caused by 2019-nCoV. CT applications also provide a fast and easy diagnosis for detecting pneumonia caused by the SARS-CoV-2 virus. The current study, aimed to compare the lung involvement of vaccinated (two-dose CoronaVac) and unvaccinated patients in the early stage of COVID-19 disease. Methods: In the current retrospective study, which included patients diagnosed with RT-PCR COVID-19 positivity (n=651) between 01 July 2021-15 September 2021, patient information was obtained from the authorized hospital of the pandemic. Data included patients' chest CT scans and whether patients had been vaccinated (two-dose CoronaVac) information. Results: The ratio of vaccination with double-dose CoronaVac in positive patients was 74.3%. The ratio of patients with normal lung appearance was 61.8%. It was determined that the ratio of involvement in both lungs of patients who were vaccinated with a double dose was significantly lower than the ratio of involvement in patients who were never vaccinated (p <0.001). Conclusion: In this study, it was determined that pneumonia cases were less common in individuals vaccinated with double-dose CoronaVac. In this study, it was also determined that the protection of the vaccine was higher in females than in males and that the protection of the double-dose CoronaVac vaccine was higher in the 50-60 age group compared to 60 older patients.

The α2C-adrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity and receptor expression in a rat model of ketamine-induced schizophrenia-like deficits.

Schizophrenia is a chronic disabling disease affecting 1 % of the population. Current antipsychotics have limited efficacy in mitigating the severity of the symptoms of the disease. Therefore, searching for new therapeutic targets is essential. Previous studies have shown that α2C-adrenoceptor antagonists may have antipsychotic and pro-cognitive effects. Therefore, the current study evaluates the behavioral and neurochemical effects of JP-1302, a selective α2C-adrenoceptor antagonist, in a model of schizophrenia-like deficits induced by sub-chronic ketamine (KET) administration. Here, we administered ketamine (25 mg/kg, i.p.) to male and female Wistar rats for eight consecutive days. On the last two days of ketamine administration, rats were pretreated with either JP-1302 (1-3-10 µmol/kg, i.p.), chlorpromazine (0.1 mg/kg, i.p.), or saline, and the behavioral tests were performed. Behaviors related to positive (locomotor activity), negative (social interaction), and cognitive (novel object recognition) symptoms of schizophrenia were assessed. Glutamate, glutamine, GABA levels, and α2C-adrenoceptor expression were measured in the frontal cortex and the hippocampus. Tyrosine hydroxylase immunocytochemical reactivity was also shown in the midbrain regions. Sub-chronic ketamine administration increased locomotor activity and produced robust social interaction and object recognition deficits, and JP-1302 significantly ameliorated ketamine-induced cognitive deficits. Ketamine induced a hyperdopaminergic activity in the striatum, which was reversed by the treatment with JP-1302. Also, the α2C-adrenoceptor expression was higher in the frontal cortex and hippocampus in the ketamine-treated rats. Our findings confirm that α2C-adrenoceptor antagonism may be a potential drug target for treating cognitive disorders related to schizophrenia.

A multi-parameter evaluation of the neuroprotective and cognitive-enhancing effects of Origanum onites L. (Turkish Oregano) essential oil on scopolamine-induced amnestic rats.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions (dementia) and represents a growing public health concern since the population in the age groups at risk is increasing. The latter raises an urgent need to translate research findings in the basic brain and behavioral sciences into anti-AD drugs and disease-modifying therapies. Origanum onites (L.), also called Turkish oregano, is a perennial and herbaceous plant species grown for centuries for medicinal, cosmetic and culinary purposes. This is the first study to investigate the putative neuroprotective and pro-cognitive activities of O. onites essential oil (OOEO) against scopolamine-induced amnesia of AD-type in Wistar albino rats. The results of behavioral tests revealed that OOEO administration was able to significantly alleviate learning and memory impairments induced by scopolamine in vivo. The observed effects could be attributed to inhibition of acetylcholinesterase activity, attenuation of oxidative stress and prevention of neuronal apoptosis in the hippocampus and frontal cortex of AD rats. Modulation of pro-inflammatory enzymes, including cyclooxygenase-2, inducible nitric oxide synthase and myeloperoxidase, might further contribute to the neuroprotective properties of OEOO, as predicted by our in silico models. These findings offer novel insights into the therapeutic potential of OEOO in patients with AD.

Epigenetic Approach to PTSD: In the Aspects of Rat Models.

Posttraumatic stress disorder (PTSD) is a stress-related mental disorder and develops after exposure to life-threatening traumatic experiences. The risk factors of PTSD included genetic factors; alterations in hypothalamic-pituitary-adrenal (HPA) axis; neurotrophic, serotonergic, dopaminergic, and catecholaminergic systems; and a variety of environmental factors, such as war, accident, natural disaster, pandemic, physical, or sexual abuse, that cause stress or trauma in individuals. To be able to understand the molecular background of PTSD, rodent animal models are widely used by researchers. When looking for a solution for PTSD, it is important to consider preexisting genetic risk factors and physiological, molecular, and biochemical processes caused by trauma that may cause susceptibility to this disorder. In studies, it is reported that epigenetic mechanisms play important roles in the biological response affected by environmental factors, as well as the task of programming cell identity. In this article, we provided an overview of the role of epigenetic modifications in understanding the biology of PTSD. We also summarized the data from animal studies and their importance during the investigation of PTSD. This study shed light on the epigenetic background of stress and PTSD.

Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats.

BACKGROUND: Methotrexate (MTX), a chemotherapeutic agent, is known to cause oral mucositis. Chitosan has been shown to have a protective effect in inflammatory animal models. This research aimed to examine the protective effect of chitosan against oral mucositis caused by MTX. METHODS AND RESULTS: Wistar albino rats were randomly divided into three groups. Control (n = 8), (saline via oral gavage for 5 days), MTX (n = 8), (60 mg/kg single dose MTX intraperitoneally on the 1st day and for the following 4 days saline via oral gavage), and MTX + chitosan (n = 8), (1st day single dose 60 mg/kg MTX intraperitoneally and followed with 200 mg/kg chitosan via oral gavage for 4 days). After 24 h of the last dose, the animals were euthanised. Blood, tongue, buccal and palatal mucosa tissues were collected. Serum interleukin 1-beta (IL1-ß), tumour necrosis factor-alpha (TNF-α), matrix metalloproteinase (MMP-1, and MMP-2) activities, tissue bcl-2/bax ratio and the expression of caspase-3 (casp-3), and casp-9 were detected. The tissues were also examined histologically. Serum TNF-α, IL1-ß, MMP-1 and MMP-2 activities and tissue casp-3 and casp-9 activities significantly increased but the bcl-2/bax ratio significantly decreased in the MTX group compared those of the control group. Histologically, diffuse inflammatory cells were observed in MTX group. However, In the MTX + chitosan group, all the values were close to those of the control group. CONCLUSION: It was demonstrated that chitosan has a protective effect against oral mucosal damage caused by MTX. Thus, it may be a candidate agent against MTX induced oral mucositis.

The Function and Expression of ATP-Binding Cassette Transporters Proteins in the Alzheimer's Disease.

Despite many years of research, radical treatment of Alzheimer's disease (AD) has still not been found. Amyloid-ß (Aß) peptide is known to play an important role in the pathogenesis of this disease. AD is characterized by three main changes occurring in the central nervous system: (1) Aß plaque accumulation that prevents synaptic communication, (2) the accumulation of hyperphosphorylated tau proteins that inhibit the transport of molecules inside neurons, and (3) neuronal cell loss of the limbic system. Mechanisms leading to Aß accumulation in AD are excessive Aß production as a result of mutations in amyloid precursor protein or genes, and impairment of clearance of Aß due to changes in Aß aggregation properties and/or Aß removal processes. Human ATP-binding cassette (ABC) transporters are expressed in astrocyte, microglia, neuron, brain capillary endothelial cell, choroid plexus, choroid plexus epithelial cell, and ventricular ependymal cell. ABC transporters have essential detoxification and neuroprotective roles in the brain. The expression and functional changes in ABC transporters contribute to the accumulation of Aß peptide. In conclusion, the review was aimed to summarize and highlight accumulated evidence in the literature focusing on the changing functions of human ABC transporter members, in AD pathogenesis and progression.

The effects of resveratrol treatment on caveolin-3 expression and Na+/K+ ATPase activity in rats with isoproterenol-induced myocardial injury.

OBJECTIVE: The present study aims to investigate the therapeutic effects of resveratrol (RES) on isoproterenol (ISO) induced myocardial injury rat model. METHODS: Catecholamine-induced heart damage was induced by ISO treatment for 30 days. The rats were divided into four groups as follows: the control group received saline, the ISO group received 5.0 mg/kg ISO, the RES group received 10 mg/kg RES, and the ISO-RES group received 10 mg/kg RES and 5 mg/kg ISO treatments for 30 days. Following echocardiographic measurements and body weight recorded, the rats were decapitated. Plasma and cardiac tissue samples obtained by decapitation were analyzed using biochemical, histopathological, molecular and immunohistochemical methods. RESULTS: In the ISO group, Na+/K+ ATPase activity and ATP content, GSH, and caveolin-3 levels were low. LDH, CK and lysosomal enzyme activities, MDA level, and MPO activity were found to be high. It was determined that GSH and MDA levels and MPO, Na+/K+ ATPase activity, ATP content caveolin-3 levels changes that arose from ISO treatment were suppressed by RES treatment. CONCLUSION: RES treatment has ameliorated all the functional and biochemical parameters. The results obtained in this study suggest that RES is a promising supplement against catecholamine exposure as it improves antioxidant defense mechanisms in the heart. In the light of above-mentioned data, RES can be assumed as a promising agent in ameliorating the oxidative injury of the myocardium.

Evaluation of the Effect of Prazosin Treatment on α-2c Adrenoceptor and Apoptosis Protein Levels in the Predator Scent-Induced Rat Model of Post-Traumatic Stress Disorder.

The predator scent-induced (PSI) stress model is a rat model used to mimic post-traumatic stress disorder (PTSD) symptoms in humans. There is growing evidence that prazosin, which blocks α-1 and is approved by the FDA as an anti-hypertensive drug, can potentially be of use in the treatment of PTSD-related sleep disorders. The aim of this study was to investigate the role of prazosin treatment on behavioral parameters (freezing time, total transitions, and rearing frequency measured from the open field; anxiety index, total entries and time spent in open arms calculated from the elevated plus maze), apoptotic proteins and α-2c-AR in fear memory reconsolidation in the PSI stress rat model. We used western blot analysis to determine the effect of prazosin (0.5 mg/kg/ip) on α-2c-AR and apoptotic protein expression changes in the frontal cortex, hippocampus, and amygdala. It was determined that in the stress group, there was increased freezing time and anxiety index, and decreased rearing frequency, total transitions, total entries, and time spent in open arms compared to the control groups. Following PSI-stress, pro-apoptotic (bax) protein expression levels increased and α-2c AR and anti-apoptotic protein (bcl-2) levels decreased in investigated all brain regions. The majority of stress-induced changes were recovered with prazosin treatment. The results of our study may potentially be useful in understanding the effect of prazosin treatment, given the fact that the amygdala, frontal cortex, and hippocampus regions are affected for stress conditions.

Evaluation of the protective effect of Myrtus communis in scopolamine-induced Alzheimer model through cholinergic receptors.

Alzheimer's disease is a progressive neurodegenerative disorder causing common health problem with increasing age. Evidences show that the key symptoms of AD are mainly caused by cholinergic system dysfunction which has a role in cognitive disorders. Cholinergic pathways especially muscarinic receptors like M1 subtype also have a major role in learning, memory, cognitive functions and emotional state. There is no available permanent treatment currently to cure AD or to change its progression. This study was designed to investigate the factors that play important role in pathogenesis of AD and to compare the effects of Galantamine treatment with effects of Myrtus communis treatment. The expression level of M1, ACh, BDNF; AChE activity, GSH level, MDA and MPO activity and AChE gene expression were investigated in scopolamine-induced rat model. Results showed that, administration of MC significantly improves the SCOP-induced reduction of latency and object recognition time; increasing BDNF, M1 and ACh receptor expression levels in the different brain regions. Additionally, MC showed an increased in AChE by enhancing GSH activity and reducing MDA level and MPO activity. In conclusion MC considered as a possible novel therapeutic approach that can be a valuable alternative way in the prevention and treatment of AD.

Protective effects of spironolactone against hepatic ischemia/reperfusion injury in rats.

OBJECTIVES: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury. MATERIAL AND METHODS: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-α), and interleukin 1beta (IL-1ß) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na+-K+-ATPase enzyme activities were analyzed to study tissue injury under light microscope. RESULTS: While IR increased AST, ALT, TNF-α, and IL-1ß levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na+K+-ATPase activity. Spironolactone administration significantly improved these values. CONCLUSION: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice.

A Special Risk Group for Hepatitis E Infection: The First Record of North Cyprus.

Hepatitis E virus (HEV) is transmitted by a fecal oral route from animals to humans following exposure to the body fluids of infected animals. We investigated the seroprevalence of anti-hepatitis E (anti-HEV) antibodies by monitoring IgG and IgM virus antibodies amongst employees in the animal industry in North Cyprus through a cross-sectional study. Samples were taken from individuals without occupational exposure to animals and from those who worked with animals (doing animal husbandry, veterinary work or butchery). Enzyme-linked immunoassays were used to detect anti-HEV IgG and IgM in the blood samples. The prevalence of anti-HEV IgG antibodies was 3.0% (12/400), while the prevalence of anti-HEV IgM antibodies was 0.25% (1/400). The prevalence of anti-HEV IgG amongst the samples received from females was approximately 2.5-fold higher than samples received from males (2.4%). Anti-HEV IgG was detected amongst 7% of animal husbandry workers and amongst 2% of veterinarians and butchers. The current findings represent the first records of HEV surveillance in Cyprus. We investigated the seroprevalence of anti-HEV by monitoring IgG and IgM virus antibodies amongst employees.Hepatitis E virus (HEV) is transmitted by a fecal oral route from animals to humans following exposure to the body fluids of infected animals. We investigated the seroprevalence of anti-hepatitis E (anti-HEV) antibodies by monitoring IgG and IgM virus antibodies amongst employees in the animal industry in North Cyprus through a cross-sectional study. Samples were taken from individuals without occupational exposure to animals and from those who worked with animals (doing animal husbandry, veterinary work or butchery). Enzyme-linked immunoassays were used to detect anti-HEV IgG and IgM in the blood samples. The prevalence of anti-HEV IgG antibodies was 3.0% (12/400), while the prevalence of anti-HEV IgM antibodies was 0.25% (1/400). The prevalence of anti-HEV IgG amongst the samples received from females was approximately 2.5-fold higher than samples received from males (2.4%). Anti-HEV IgG was detected amongst 7% of animal husbandry workers and amongst 2% of veterinarians and butchers. The current findings represent the first records of HEV surveillance in Cyprus. We investigated the seroprevalence of anti-HEV by monitoring IgG and IgM virus antibodies amongst employees.

Protective effects of St. John's wort in the hepatic ischemia/reperfusion injury in rats.

OBJECTIVES: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury. MATERIAL AND METHODS: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis. RESULTS: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1ß levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity. CONCLUSION: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.

Protective effect of silk fibroin in burn injury in rat model.

Activation of pro-inflamatuar pathways play major role in formation of major complications as a result of burns. This study was planned to investigate the protective effect of Silk Fibroin in lung injury caused by burn in the experimental rat model. After rinsing the skin of rats under ether anesthesia, the exposed back region, covers 30% of the total body, was kept in the 90°C water bath for 10s. The control rats were kept in the 25°C water bath for 10s. Immediately after burning process, silk fibroin was administered orally at a dose of 600mg/kg. After 24h following burning from all groups the levels of TNF-α, IL-1ß in blood samples and the MDA, GSH and the activity of MPO were determined from taken lung tissues. Moreover, the expression of Bcl-2/Bax, Caspase-3 and Caspase-9 were determined. Significant increase in TNF-α, IL-1ß, Casp-3 and Casp-9 levels were observed in the Silk Fibroin-treated burn group (p<0.05) whereas for ratio of Bcl-2/Bax, a significant reduction was observed compared to control group (p<0.05). Increased levels of TNF-α, IL-1ß, Caspase-3 and Caspase-9 in Silk Fibroin-treated burn groups were found to be reversed. Silk fibroin can be an effective biomaterial in diminishing burn injury in tissue and apoptosis.

Protective effect of betaine against burn-induced pulmonary injury in rats.

BACKGROUND: This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma. METHODS: Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90°C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25°C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+/K+-ATPase activity, in addition to histological analysis. RESULTS: Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury. CONCLUSION: Treatment of rats with betaine significantly restored GSH level and Na+/K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue.

D-Cycloserine acts via increasing the GluN1 protein expressions in the frontal cortex and decreases the avoidance and risk assessment behaviors in a rat traumatic stress model.

D-cycloserine (DCS), an FDA approved anti-tuberculosis drug has extensively been studied for its cognitive enhancer effects in psychiatric disorders. DCS may enhance the effects of fear extinction trainings in animals during exposure therapy and hence we investigated the effects of DCS on distinct behavioral parameters in a predator odor stress model and tested the optimal duration for repeated daily administrations of the agent. Cat fur odor blocks were used to produce stress and avoidance and risk assessment behavioral parameters were used where DCS or saline were used as treatments in adjunct to extinction trainings. We observed that DCS facilitated extinction training by providing further extinction of avoidance responses, risk assessment behaviors and increased the contact with the cue in a setting where DCS was administered before extinction trainings for 3 days without producing a significant tolerance. In amygdala and hippocampus, GluN1 protein expressions decreased 72h after the fear conditioning in the traumatic stress group suggesting a possible down-regulation of NMDARs. We observed that extinction learning increased GluN1 proteins both in the amygdaloid complex and the dorsal hippocampus of the rats receiving extinction training or extinction training with DCS. Our findings also indicate that DCS with extinction training increased GluN1 protein levels in the frontal cortex. We may suggest that action of DCS relies on enhancement of the consolidation of fear extinction in the frontal cortex.

The change in muscarinic receptor subtypes in different brain regions of rats treated with fluoxetine or propranolol in a model of post-traumatic stress disorder.

This study shows the possible contribution of muscarinic receptors in the pathophysiology of post-traumatic stress disorder. Sprague-Dawley rats of both sexes were exposed to dirty cat litter (trauma) for 10 min and the protocol was repeated 1 week later with a trauma reminder (clean litter). The rats also received intraperitoneal fluoxetine (2.5, 5 or 10 mg/kg/day), propranolol (10 mg/kg/day) or saline for 7 days between two exposure sessions. Functional behavioral experiments were performed using elevated plus maze, following exposure to trauma reminder. Western blot analyses for M(1), M(2), M(3), M(4) and M(5) receptor proteins were employed in the homogenates of the hippocampus, the frontal cortex and the amygdaloid complex. The anxiety indices increased from 0.63±0.02 to 0.89±0.04 in rats exposed to the trauma reminder. The freezing times were also recorded as 47±6 and 133±12 s, in control and test animals respectively. Fluoxetine or propranolol treatments restored the increases in the anxiety indices and the freezing times. Female rats had higher anxiety indices compared to males. Western blot data showed increases in M(2) and M(5) expression in the frontal cortex. Expression of M(1) receptors increased and M(4) subtype decreased in the hippocampus. In the amygdaloid complex of rats, we also detected a down-regulation of M(4) receptors. Fluoxetine and propranolol only corrected the changes occurred in the frontal cortex. These results may imply that muscarinic receptors are involved in this experimental model of post-traumatic stress disorder.