INTRODUCTION:Neurosecretory cells of insects synthesize Adipokinetic Hormone (AKH). Previous studies indicated that AKH improves memory functions. This study aimed to explore the effects of AKH on learning and memory in an Alzheimer's disease model. METHODS:Morris Water Maze (MWM), Passive Avoidance (PA), and Modified Elevated Plus Maze (mEPM) tests were conducted in BALB/c mice. Initially, each group consisted of 8 to 9 animals; in total, 120 animals were used in this study. The groups included control, Ani-AKH (1 and 2 mg/kg), Lia-AKH (1 and 2 mg/kg), Pht-HrTH (1 and 2 mg/kg), Scopolamine (1 mg/kg), and Scopolamine combinations. Hormones were given for 6 days in the MWM test to evaluate learning and memory before the second trial in the PA test for memory assessment and after the first trial in the mEPM test to examine consolidation. RESULTS:In the MWM test, Ani-AKH and Pht-HrTH reduced escape latency compared to the scopolamine group (p<0.05). During the probe trial, Ani-AKH increased time in the escape platform quadrant (p<0.5) and reversed scopolamine's effects (p<0.001). Lia-AKH and Pht-HrTh did not affect time in the quadrant but reversed scopolamine's effects (p<0.01). In the PA test, Ani- AKH reversed scopolamine's effects (p<0.5), while Lia-AKH did so in the mEPM test (p<0.01). The control group showed strong muscarinic receptor staining, while the scopolamine group did not. Ani-AKH and Lia-AKH showed moderate to strong receptor staining, indicating partial restoration. DISCUSSION:AKH and its analogs may enhance memory function by modulating cholinergic pathways, particularly through the partial restoration of muscarinic receptor activity. These results underscore their potential as investigational therapeutics for neurodegenerative disorders characterized by cognitive decline. CONCLUSION:Our study indicates that AKH may help reduce memory impairments, though the effects depend on the specific assessment methods used in the tests.

OBJECTIVE: It has been previously shown that brain-derived neurotrophic factor is linked with various types of cancer. Brain-derived neurotrophic factor is found to be highly expressed in multiple human cancers and associated with tumor growth, invasion, and metastasis. Adipokinetic hormones are functionally related to the vertebrate glucagon, as they have similar functionalities that manage the nutrient-dependent secretion of these two hormones. Migrasomes are new organelles that contain numerous small vesicles, which aid in transmitting signals between the migrating cells. Therefore, the aim of this study was to investigate the effects of Anax imperator adipokinetic hormone on brain-derived neurotrophic factor expression and ultrastructure of cells in the C6 glioma cell line. METNODS: The rat C6 glioma cells were treated with concentrations of 5 and 10 Anax imperator adipokinetic hormone for 24 h. The effects of the Anax imperator adipokinetic hormone on the migrasome formation and brain-derived neurotrophic factor expression were analyzed using immunocytochemistry and transmission electron microscope. RESULTS: The rat C6 glioma cells of the 5 and 10 mu M Anax imperator adipokinetic hormone groups showed significantly high expressions of brainderived neurotrophic factor and migrasomes numbers, compared with the control group. CONCLUSION: A positive correlation was found between the brain-derived neurotrophic factor expression level and the formation of migrasome, which indicates that the increased expression of brain-derived neurotrophic factor and the number of migrasomes may be involved to metastasis of the rat C6 glioma cell line induced by the Anax imperator adipokinetic hormone. Therefore, the expression of brain-derived neurotrophic factor and migrasome formation may be promising targets for preventing tumor proliferation, invasion, and metastasis in glioma.

Amaç: Önceki çalışmalarımızda adipokinetik hormonun (AKH) farelerde antidepresan, anksiyolitik, analjezik etkilerini, nörotrofik faktörleri ve nörojenezi artırdığını gösterdik. Önceki çalışmamızda, AKH’nun sıçanlara intraperitoneal uygulanmasından sonra diğer çalışmalarla desteklendiği şekilde piroglutamil peptidleri içeren AKH metabolitlerinin kan-beyin bariyerini geçtiğini hipotez ettik. Gereç ve Yöntemler: Bu çalışmada, iki piroglutamil peptidin öğrenme-bellek üzerine etkisini modifiye yükseltilmiş artı labirent testinde (mYAL) ve pasif sakınma testinde hem naif farelerde hem de skopolaminle indüklenen bellek bozukluğu üzerine etkisini incelemeyi amaçladık. Skopolamin (1 mg/kg) ile piroglutamil peptid olarak piroglutamik asid-valin (pGlu-Val; 10 ve 20 mg/kg), piroglutamik asid-lösin (pGlu-Leu; 10 ve 20 mg/kg) kullandık. Bulgular: mYAL testinde dipeptidlerin naif farelerde geçiş süresi-2 üzerine anlamlı etkisi yoktu. Skopolamin kısmi olarak ikinci denemede geçiş süresi-2’yi artırırken, bu etki pGlu-Leu (10 ve 20 mg/kg; p

Aims: Antipsychotic drugs are known to be commonly associated with sexual dysfunction. The aim of this study to investigate the effects of sertindole, asenapine and ziprasidone on serotonin (5-HT), noradrenaline (NA), adenosine triphosphate (ATP) and potassium chloride (KCl)-induced contractions of the isolated vas deferens in mice. Study design: All the drugs were administered intraperitoneally (i.p.) in a volume of 0.1 ml per 10 g body weight of mice. Place and Duration of Study: Department of Pharmacology, Kocaeli University, Animal Research Center, between May 2018 and August 2019. Methodology: The mice were randomly divided into groups (n=7) as follows: saline; sertindole 1.3 mg/kg; sertindole 2.5 mg/kg; asenapine 0.05 mg/kg; asenapine 0.075 mg/kg; ziprasidone 1 mg/kg; ziprasidone 2 mg/kg once daily for 21 days. Mice receiving only the vehicle (0.9% saline, i.p.) served as control group. After 21 days of treatment, the effects of drugs were investigated on 5-HT, NA, ATP and KCl-induced contractions of isolated vas deferens. Results: The results showed that serotonin-induced contractions of vas deferens were affected by the chronic treatments of sertindole, asenapine and ziprasidone, however these drugs had no significant effect on NA, ATP, and KCl-induced contractions of mice vas deferens. Conclusion: Serotonergic receptors may contribute to changes in vas deferens contractions in mice with chronic treatment of sertindole, asenapine and ziprasidone. Thus, our results may explain one of the causes of sexual dysfunction of sertindole, asenapine and ziprasidone.

Objective: Overactive bladder (OAB) constitutes the majority of childhood incontinence causes. Oxybutynin is an antimuscarinic agent frequently used for children in the treatment of OAB. This study aimed to investigate the effects of an antimuscarinic drug oxybutynin on learning and memory. Materials and Methods: We assessed the effects of oxybutynin on learning and memory functions using the Passive Avoidance (PA) and the Morris Water Maze (MWM) Test in mice. Results: Oxybutynin treatment (1 mg/kg, 2 mg/kg, and 4 mg/kg) did not show a significant difference in the retention time on the second day compared to the control and oxybutynin (4 mg/kg) significantly prolonged the retention time in scopolamine-treated mice. In the MWM Test, oxybutynin (1 mg/kg, 2 mg/kg, and 4 mg/kg) has no effect on the time spent in the target quadrant. Scopolamine (0.6 mg/kg) alone significantly reduced time spent in the target quadrant, but oxybutynin (4 mg/kg) significantly prolonged time spent in the target quadrant in scopolamine-treated mice. Also, scopolamine significantly increased the mean distance to the escape platform, while oxybutynin (4 mg/kg) significantly decreased the mean distance to the escape platform in scopolamine-treated mice. Conclusion: In our study, oxybutynin did not affect learning and memory, but it plays a role ameliorating the learning and memory deficits. The results of this study show that the use of oxybutynin in patients with OAB does not affect learning and memory.

Objective: Erectile dysfunction is a usual side effect of antipsychotic medications; this causes patients to avoid using drugs. The aim of this study to investigate the effects of iloperidone, paliperidone and loxapine on serotonin (5-HT), noradrenaline (NA), adenosine triphosphate (ATP) and potassium chloride (KCl)-induced contractions of the vas deferens in mice.Materials and Methods: The mice were randomly divided into experimental groups and treated by ip injection of drugs for 21 days. After the treatment, the effects of drugs were investigated on 5-HT, ATP, NA and KCl-induced contractile responses in the epididymal and prostatic portions of mice vas deferens strips. Results: 5-HT-induced contractile responses were significantly increased while ATP-induced contractile responses were significantly decreased in the both portions of the vas deferens obtained from the iloperidone, paliperidone and loxapine-treated groups. However, these drugs had no significant effect on NA- and KCl-induced contractions of mice vas deferens. Conclusion: These results showed that serotonin and ATP-induced contractions of vas deferens were affected by the chronic treatments of iloperidone, paliperidone, and loxapine. In mice chronically treated with these drugs, serotonergic and purinergic receptors may contribute to changes in vas deferens contractions that cause erectile dysfunction.

Objective: The bladder normally shows no contractility or activity during the filling phase. In the overactive urinary bladder, spontaneous contractions and detrusor instability are seen in the filling phase and urinary incontinence occurs. This study aims to demonstrate the effects of first-generation antipsychotic haloperidol and second-generation antipsychotics olanzapine, risperidone, and clozapine on mice isolated bladder using the organ bath system. Materials and Methods: 63 male inbred mice were divided as saline, haloperidol 0.125 mg/kg, haloperidol 0.25 mg/kg, olanzapine 1 mg/kg, olanzapine 2 mg/kg, risperidone 0.25 mg/kg, risperidone 0.5 mg/kg, clozapine 1.25 mg/kg and clozapine 2.5 mg/kg groups. Mice were treated with drugs for 21 days. Then, the effects of drugs were investigated on isoproterenol-induced relaxation responses of carbachol-induced contractions in isolated detrusor strips. Results: We showed that carbachol-induced contractions relaxed by isoproterenol and papaverine in mice detrusor strips obtained from olanzapine, risperidone, and clozapine treated groups. There were no significant differences in KCl-induced contractile responses among the groups.Conclusion: Olanzapine, risperidone, and clozapine increased the isoproterenol-induced relaxations of the detrusor muscle that increased the bladder capacity. These drugs might be clinically useful for the treatment of overactive urinary bladder in patients that should use antipsychotic drugs.

Mirabegron is the first b3-adrenoceptor agonist to enter clinical practice and has been approved for the treatment of symptoms of OAB. The aim of this study is to investigate whether the mirabegron has an effect on depression, anxiety, learning, and memory. We investigated the effects of mirabegron on depression, anxiety, learning and memory by using forced swimming test, elevated plus maze test, passive avoidance and Morris water maze in mice. Imipramine and mirabegron (3, 6 and 9 mg/kg) significantly reduced immobility time in forced swimming test. Diazepam and mirabegron (3, 6 and 9 mg/kg) significantly increased the time spent in open arms and the number of entries to the open arms in elevated plus maze test. Furthermore, cognitive performance impaired with scopolamine has been significantly improved with 9 mg/kg mirabegron. Mirabegron (6 and 9 mg/kg) significantly increased the time spent in the target quadrant in naive mice. While scopolamine significantly increased the swimming speed, mirabegron (9 mg/kg) significantly decreased the swimming speed in scopolamine-treated mice. Mirabegron might be clinically useful for the treatment of OAB in elderly patients that should use drugs against depression and anxiety, without disrupt learning and memory.

Background: Overactive bladder (OAB) is characterized by urinary symptoms such as frequent urination, urgency, urinary incontinence, and nocturia. Tolterodine is a drug specially developed for the treatment of overactive bladder. The aim of present study is to evaluate the effects of tolterodine on depression, anxiety, learning and memory to understand if tolterodine may be effective in OAB caused mood and cognitive disorders. Methodology: Study Design: All the drugs were given intraperitoneally (i.p.), 30 min before the experiment. Here, we investigated the effects of tolterodine (0.3, 1, 3 mg/kg) on depression, anxiety, learning and memory by using forced swimming test, elevated plus maze test, passive avoidance, and Morris water maze, respectively in mice. Locomotor activity was evaluated by open field test. Place and Duration of Study: Department of Pharmacology and Department of Urology, Sakarya University, Animal Research Center, between August 2019 and September 2020. Results: All doses of tolterodine dose-dependently reduced immobility time, compared to saline group. Tolterodine (1, 3 mg/kg) prolonged the time spent in open arms compared to saline group. Tolterodine (3 mg/kg) significantly increased the number of entries into the open arms. Tolterodine had no effect on learning and memory performance of normal mice; however, tolterodine (3 mg/kg) significantly ameliorated learning and memory disruption induced by scopolamine. Conclusion: Our results demonstrate that tolterodine prevented experimentally induced depression and anxiety, improved memory and learning of naive animals, and reversed memory and learning impairment with scopolamine. Further preclinical and clinical studies with tolterodine should be done to support all these hypothesis and patients with OAB who need antidepressant and anxiolytic therapy may be treated with single drug instead of more than one drug in the future.

Öz: Amaçlar: Antipsikotik ilaçların yaygın olarak cinsel işlev bozukluğu ile ilişkili olduğu bilinmektedir. Ancak atipik antipsikotik ilaçların bu etkilerine ilişkin çalışmalar oldukça sınırlıdır. Bu çalışmanın amacı, fare vas deferensinin serotonin (5-HT), noradrenalin (NA), adenozin trifosfat (ATP) ve potasyum klorür (KCl) ile indüklenen kasılmaları üzerine siyamemazin, blonanserin ve nemonaprid'in etkilerini araştırmaktır. Gereç ve Yöntemler: Bu çalışmada erkek kendi içinde yetiştirilmiş fareler kullanılmıştır. Fareler rastgele deney gruplarına (n=7) şu şekilde ayrıldı: salin; siyamemazin 0,25 mg/kg; siyamemazin 0,50 mg/kg; blonanserin 0,5 mg / kg; blonanserin 1 mg/kg; nemonaprid 0,5 mg / kg; nemonaprid 1 mg / kg. Farelere, 21 gün boyunca ilaçlar intraperitoneal olarak uygulandı. 21 gün boyunca %0.9 salin alan fareler kontrol grubunu oluşturdu. 21 günlük tedaviden sonra, ilaçların etkileri, fare vas deferensinin epididimal ve prostatik bölümlerine 5-HT, NA, ATP ve KCl'nin neden olduğu kasılma tepkileri araştırıldı. Bulgular: Siyamemazin ve blonanserin ile tedavi edilen fare vas deferenslerinin hem epididimal ve hem de prostatik kısımlarında, 5-HT ile indüklenen kasılma tepkileri anlamlı bir şekilde arttı. Ayrıca, siyamemazin, blonanserin ve nemonaprid uygulanan fare vas deferenslerinin prostatik ve epididimal kısımları; NA, ATP, KCl ile indüklenen kasılmaları önemli ölçüde değiştirmedi. Sonuçlar: Bu sonuçlar, vas deferens'in serotonin kaynaklı kasılmalarının, kronik siyamemazin ve blonanserin tedavilerinden etkilendiğini, ancak nemonapridden etkilenmediğini gösterdi. Ancak bu ilaçların NA, ATP ve KCl ile indüklenen kasılmalar üzerinde önemli bir etkisi yoktu. Serotonerjik reseptörler, kronik ciamemazin ve blonanserin tedavisi gören farelerde vas deferens kasılmalarındaki değişikliklere katkıda bulunabilir. Bu nedenle, sonuçlarımız, siyamemazin ve blonanserin'in neden olduğu cinsel işlev bozukluğunun nedenlerinden birini açıklayabilir.

Objective: Insect Adipokinetic Hormones (AKH) play role in sugar and lipid mobilization and support the production of energy for the flight and movement of insects. In our previous studies, we showed that AKH had antidepressant, anxiolytic, and analgesic effects in mice and increased neurotrophic factors and neurogenesis in mice, and had beneficial effects in olfactory bulbectomy and posttraumatic stress disorder rat models. In our previous study, we hypothesized that metabolites of AKH, including pyroglutamic acid and pyroglutamyl peptides, pass the blood-brain barrier after intraperitoneal administration of AKH in rats, which is supported by other studies. Methods: In this study, we aimed to investigate the effects of three pyroglutamyl peptides on depression, anxiety, and analgesia in the Forced Swimming Test (FST), Elevated Plus Maze (EPM) test, and hot plate test in mice. We used L-pyroglutamic acid (pGlu; 50 mg/kg), pyroglutamic acid-valine (pGlu-Val; 10 mg/kg), pyroglutamic acid-leucine (pGlu-Leu; 10 mg/ kg) and pyroglutamic acid-valine-aspartate-phenylalanine (pGlu-Val-Asp-Phe; 10 mg/kg) as pyroglutamyl peptides. Results: In FST, all the peptides decreased immobility time, showing that these peptides had antidepressant-like effects. In the EPM test, none of the peptides had a significant effect, but tetrapeptide partially increased both % time spent in the open arm and % entry into the open arm. In the hot plate test, both dipeptides significantly increased latency of licking the arm showing that these dipeptides had analgesic effects. In the open field test, none of the studied peptides altered the total number of crossings compared to the control treatment. Conclusion: In conclusion, we found that pyroglutamyl peptides had preclinical beneficial effects on animal behavior in mice.

Aims: Benign prostatic hyperplasia (BPH) is common urological disease, is characterized by lower urinary tract syndrome, usually associated with sexual dysfunctions. The aim of present study is to investigate the effects of terazosin, silodosin and alfuzosin which are the main treatment options for BPH on depression and anxiety to understand whether these drugs may be effective in BPH caused mood disorders. Study Design: All the drugs were given intraperitoneally (i.p.) in a volume of 0.1 ml per 10 g body weight of mice. Drugs were given 30 min before the experiment. We investigated the effects of terazosin, silodosin and alfuzosin on depression and anxiety, in mice. Place and Duration of Study: Sample: Department of Pharmacology and Department of Urology, Sakarya University, Animal Research Center, between June 2019 and September 2020. Methodology: Here, we examined the effects of terazosin (0.5, 1, 2 mg/kg), silodosin silodosin (1, 3, 10 mg/kg) and alfuzosin (3, 6 and 9 mg/kg) on depression and anxiety by using forced swimming test and elevated plus maze test, respectively, in mice (n:96). Additionally, the locomotor activity was evaluated by open field test. Results: All doses of terazosin, alfuzosin and silodosin significantly increased immobility time, compared to saline group. Silodosin and alfuzosin prolonged the time spent in open arms but terazosin decreased the time spent in open arms compared to saline group. Terazosin, silodosin (1 and 3 mg/kg) and alfuzosin (3 and 6 mg/kg) did not have any effect on the number of entries into the open arms while silodosin (10 mg/kg) and alfuzosin (9 mg/kg) increased the number of entries into open arms. Conclusion: We found that silodosin and alfuzosin had antidepressant and anxiolytic-like effects, while terazosin had depressant and anxiogenic effects. Patients with BPH who need antidepressant and anxiolytic treatment can be treated with a single drug instead of multiple medications.

Objective: Ziprasidone, aripiprazole, blonanserin, cyamemazine, and nemonapride are atypical antipsychotic drugs used for the treatment of schizophrenia. This study aimed to identify the effects of these atypical antipsychotic drugs in mice isolated bladder using the organ bath systemMaterials and Methods: The mice were injected intraperitoneally with drugs for 21 days. The effects of drugs were investigated on isoproterenol-induced relaxation responses of carbachol-induced contractions in isolated detrusor strips. The detrusor strips were stimulated with KCl, then tissues were washed for a further 30 min and precontracted with a submaximal concentration of carbachol. After the contraction reached a plateau, cumulative concentration-response curves to isoproterenol were obtained.Results: We showed that carbachol-induced contractions dose-dependently relaxed by isoproterenol in mice detrusor strips obtained from ziprasidone, aripiprazole, blonanserin, and cyamemazine but not nemonapride treated group. However, none of the drug treatments had any effect KCl responses of mice's bladder.Conclusion: Ziprasidone, aripiprazole, blonanserin, and cyamemazine but not nemonapride increased the isoproterenol-induced relaxations of the detrusor smooth muscle indicates that it can increase the bladder capacity. We demonstrate that four drugs may represent a potential treatment for overactive bladder. They might be clinically useful for the treatment of overactive bladder in patients that should use antipsychotics.

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.

SARS-CoV-2 virüsü Aralık 2019’da ortaya çıkmış ve başlangıçta Çin, Japonya ve Güney Kore olmak üzere tüm dünyada hızlıca yayılmıştır. Bilim insanları virüse spesifik antiviral bulmak için çabalamaktadır. Koronavirüs hastalığı 2019 (COVID-19) tedavisinde hidroksiklorokin, azitromisin, favipiravir, remdesivir, lopinavir/ritonavir gibi ilaçlar denenmektedir. Dünyada bu ilaçlar halen klinik çalışmalardan geçmektedir, bazı umut veren sonuçlara ulaşılmıştır. Bu makalede SARS-CoV-2’ye karşı güçlü etkinliği olan ilaçlar özetlenmektedir.

Objective: Adipokinetic hormone (AKH) plays a role in sugar and lipid metabolism in insects. Previous studies of AKH showed memory improvements in a schizophrenia rat model that displayed memory impairment and reduced depression in a rat olfactory bulbectomy model. In this study, we investigated the effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on brain neurotransmitter levels and brain neurochemistry in a schizophrenia rat model. Materials and Methods: We administered AKH/RPCH peptides for 4 days sub-chronically, both in naive rats and also in the MK-801-induced schizophrenia rat model. Liquid chromatography-mass spectrometry apparatus was used for targeted and untargeted analysis of rat neurochemistry. Results: Increased brain glutamate levels characteristic of MK-801 peptide-treated rats were significantly reduced by AKH. Furthermore, AKH also increased brain dopamine levels in both naive and MK-801 rats. Metabolomic studies have shown that AKH affects lipid and glutamate metabolism, while hypertrehalosaemic hormone plays a role in sugar metabolism and inflammation. Conclusion: According to our results, AKH might affect dopaminergic and glutamatergic systems and reverse the effects of MK-801, possibly affecting NMDA receptors.

Objective: Schizophrenia, is an important brain neurodevelopmental disorder observed in 1% of the global population. Classical antipsychotics cause extrapyramidal side effects and are less effective on the negative symptoms of schizophrenia. New-generation atypical antipsychotics have been developed as alternatives to typical antipsychotics for more effective on negative symptoms of schizophrenia such as mood and memory disorders or safer therapy. Olanzapine and clozapine are new atypical antipsychotics that are frequently used in clinics. Methods: Effects of olanzapine and clozapine on depression and anxiety in the forced swimming (FST) and elevated plus maze (EPM) test were examined in mice. Since there is a growing interest in the role of neutrophins in the pathophysiology of schizophrenia, the effects drugs on the expression levels of brain neurotrophic factors (BDNF, CREB, NGF, synapsin and FGF2) in the hippocampus of mice were also investigated. Mice were treated chronically and intraperitoneally with olanzapine (1 and 2 mg/kg,) or clozapine (1.25 and 2.5 mg/kg) for 10 days and 60 and 30 minutes respectively before FST and EPM tests on the 11th day. Results: In the FST test, clozapine (2.5 mg/kg; p<0.05) significantly decreased immobility time while olanzapine (1ve 2 mg/kg; p>0.05) had no significant effect on this parameter. In the EPM test, olanzapin (2 mg/kg; p<0.01) and clozapine (1.25 ve 2.5 mg/kg; p<0.01 and p<0.05 respectively) significantly increased both % time spent in open arms (p<0.001) and % open arm entries (p<0.01). Clozapine up-regulated the expression of BDNF, CREB, NGF synapsin and FGF2 in the mice hippocampus. Olanzapine up-regulated the expression of NGF, synapsin and FGF2 but it down-regulated the expression of BDNF and CREB. Conclusion: Clozapine seems to possess superior effects compared to olanzapine on negative semptoms of schizophrenia since it up-regulates more neurotrphic factors than olanzapine in the brain.

Objective: One of the most important problems of schizophrenic patients is the impairment of cognitive functions. Methods: The aim of this study was to investigate the effects of haloperidol, asenapine and paliperidone on spatial learning and memory using the Morris water maze (MWM) and radial arm maze (RAM) tests; moreover the effects of haloperidol, asenapine, and paliperidone on MK-801 induced cognitive dysfunction were also evaluated in mice. Results: Both asenapine (0.05 mg/kg) and paliperidone reversed MK-801 induced increment in escape latency in 2nd, 3rd, and 4th acquisition sessions while haloperidol failed to reverse MK-801 induced this effect. Time spent in escape platform's quadrant significantly decreased while the mean distance to platform significantly increased in MK-801 group in the probe trial of MWM test and administration of asenapine and paliperidone significantly reversed MK-801 induced these effects while haloperidol had no effect. MK-801 significantly increased the speed of the animals in probe trial of the MWM test while both asenapine and paliperidone reversed this effect. In the RAM test, MK-801 significantly increased the number of errors in the retention trial and haloperidol failed to reverse this effect. Both asenapine (0.075 mg/kg) and paliperidone reversed MK-801-induced increment in a number of errors and improved MK-801 induced prolongation in latency. Conclusions: The results of this study revealed that MK-801 exerted spatial memory impairment in MWM and RAM tests; haloperidol failed to improve MK-801 induced memory deterioration in mice. Moreover both asenapine and paliperidone improved MK-801 induced spatial learning and memory impairment in the MWM and RAM tests.

Several olfactory receptors (ORs) have been characterized outside the olfactory neuroepithelium in neuronal and non-neuronal tissues, where they were implicated in the recognition of diverse chemical signals. ORs have been found to regulate melanogenesis in skin melanocytes, and OR expression has been found in the human brain nigrostriatal dopaminergic neurons, where production of melanin occurs as neuromelanin and can change with age; OR expression is downregulated in Parkinson’s disease. Therefore, we propose several odorants as new functional ligands to ORs expressed in non-olfactory pigmented cells as dopaminergic neurons and melanocytes, where, by acting on cAMP-induced melanin production, they could help to counteract melanogenic and neurodegenerative dysfunctions, including melanoma and Parkinson’s disease.