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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: 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.

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.

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.

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., Amaç: Erektil disfonksiyon, antipsikotiklerin olağan bir yan etkisidir; bu da hastaların ilaç kullanmaktan kaçınmasına neden olur. Bu çalışmanın amacı iloperidon, paliperidon ve loksapin'in farelerde serotonin (5-HT), noradrenalin (NA), adenozin trifosfat (ATP) ve potasyum klorür (KCl) ile indüklenen vas deferens kasılmaları üzerine etkilerini araştırmaktır.Materyal ve Metot: Fareler rastgele deney gruplarına ayrıldı ve 21 gün boyunca ip enjeksiyonu ile tedavi edildi. Tedaviden sonra, ilaçların farelerin vas deferens şeritlerinin epididimal ve prostatik bölümlerinde 5-HT, ATP, NA ve KCl ile indüklenen kasılma tepkileri üzerindeki etkileri araştırıldı.Bulgular: İloperidon, paliperidon ve loksapin ile tedavi edilen gruplardan elde edilen vas deferensin her iki bölümünde 5-HT ile indüklenen kasılma tepkileri önemli ölçüde artarken ATP ile indüklenen kasılma tepkileri önemli ölçüde azaldı. Bununla birlikte, bu ilaçların, fare vas deferens'in NA ve KCl ile indüklenen kasılmaları üzerinde önemli bir etkisi olmamıştır. Sonuç: Bu sonuçlar, iloperidon, paliperidon ve loxapin'in kronik tedavilerinden serotonin ve ATP kaynaklı vas deferens kasılmalarının etkilendiğini göstermiştir. Bu ilaçlarla kronik olarak tedavi edilen farelerde, serotonerjik ve purinerjik reseptörler, erektil disfonksiyona neden olan vas deferens kasılmalarındaki değişikliklere katkıda bulunabilir.

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.

Objective: Several classes of prescription drugs contribute to the sexual dysfunction in men that have been found especially in the antipsychotic drugs. Varieties of mechanisms are likely to contribute to the antipsychotic-related sexual dysfunction including hyperprolactinemia and antagonism of some neurotransmitter receptors. Implications for future research, atypical antipsychotics should be strongly taken into account. Material and Method: Male mice were treated by intraperitoneal injection (IP injection) of drugs for 21 days. The effects of saline, quetiapine, olanzapine, and risperidone were investigated on serotonin, noradrenaline (NA), adenosine triphosphate (ATP) and potassium chloride (KCl) which induced contractions of the vas deferens. Results: Serotonin-induced contractile responses were significantly increased in the epididymal and prostatic portion of the vas deferens obtained from the risperidone-treated group. The Emax value for serotonin was significantly higher in prostatic and epididymal portions of the mice vas deferens obtained from the risperidone-treated group than the control group. However, olanzapine and quetiapine treatment had no effect on serotonin responses in both epididymal and prostatic portions of the mice vas deferens. The risperidone treatment significantly inhibited both noradrenaline and ATP-induced contractions of the prostatic and epididymal portions of the mice vas deferens. There were no significant differences in KCl-induced contractile responses among the groups. Conclusion: It can be concluded that only risperidone could impair sexual competence in the male mice. Serotonergic, noradrenergic and purinergic receptors may contribute to the changes in vas deferens contractions in mice with chronic treatment of risperidone but not olanzapine and quetiapine. This study will help clinicians make a purpose-oriented choice of which antipsychotic drug to use.

Bu calismada, farelerde desipramin, venlafaksin ve bupropiyonun depresyon ve anksiyete uzerine etkilerini arastirmayi amacladik. Klasik trisiklik antidepresan, desipramin, serotonin-norepinefrin geri alim inhibitoru venlafaksin ve ikinci jenerasyon antidepresan bir ajan olan noradrenalin ve dopamin gerialim inhibitoru bupropion kullandik. Imipramin (30 mg/kg), desipramin (7,5 mg/kg ve 15 mg/kg), venlafaksin (4 mg/kg ve 8 mg/kg) ve bupropion (20 mg/kg ve 40 mg/kg) FST'de hareketsizlik zamanini onemli olcude doza bagli bir sekilde azaltti. Ayrica bupropion (40 mg/kg) da imipramine gore anlamli derecede etkiliydi. Diazepam (2 mg/kg), desipramin (7.5 mg/kg ve 15 mg/kg), venlafaksin (4 mg/kg ve 8 mg/kg) ve bupropion (20 mg/kg ve 40 mg/kg) EPM'de acik kollarda kalis suresini onemli olcude doza bagli arttirdi. Diazepam (2 mg / kg), desipramin (7,5 mg/kg ve 15 mg/kg), venlafaksin (8 mg/kg) ve bupropion (20 mg/kg ve 40 mg/kg) acik kola giris sayisini da artirdi. Ayrica bupropion (40 mg/kg) diazepamdan anlamli derecede daha etkiliydi. Desipramin, venlafaksin ve bupropion (20 mg/kg), imipraminin etkilerinden onemli olcude farkli olmayan antidepresan benzeri etkilere neden olmustur. Bunun yaninda bupropion (40 mg/kg) antidepresan benzeri etki gostermistir ve bu etkiler imipraminden daha gucludur. Benzer sekilde, desipramin, venlafaksin ve bupropion (20 mg/kg), diazepamin etkilerinden onemli olcude farkli olmayan anlamli anksiyolitik benzeri etkiler gostermislerdir. Ayrica bupropion (40 mg / kg) anlamli anksiyolitik benzeri etkiler gostermis ve bu etkiler diazepamdan daha gucludur.

Background: Smoking is a hallmark preventable health issue worldwide. The role of smoking in the aetiology of prostate cancers remains a lack of consensus. Methods and material: 100 male albino Wistar rats were used. The smoking group (n=40) was exposed to cigarette smoke for 2 hours per day for 8 weeks. The rest were set aside as a control group (n=60). At the end of 8 weeks, the rats were sacrificed and haemoglobin and serum cotinine values were measured. The prostate glands were excised and dorsolateral strips were prepared for in vitro examination. After application of 80 mM KCl, carbachol, and phenylephrine, respectively, contraction values were obtained and calculated in grams. Prostate tissues were stained using p53, bcl-2, cyclin D, and c-erb-B2 immunohistochemical and Hematoxylin-Eosin gram staining. Results: In the smoking group, the mean haemoglobin value was found out as 16.5 mg/dl, and 11.5 mg/dl in the control group respectively. The cotinine values were determined to be 76.43 ng/ml in the smoking group and

Sexual dysfunction is a common condition in patients taking antipsychotics and is the most bothersome symptom and adverse drug effect, resulting in a negative effect on treatment compliance. Pharmacology research into human ejeculatory disorders is limited to clinical studies with registered drugs affecting the ejaculation process; therefore, animal research has become the need. We aimed to investigate the effects of haloperidol, clozapine and aripiprazole on serotonin, noradrenaline, adenosine triphosphate (ATP) and potassium chloride (KCl)-induced contractions of the vas deferens in order to evaluate the effect of haloperidol, clozapine and aripiprazole on the contraction of the vas deferens. Male inbred BALB/c ByJ mice aged 7 weeks upon arrival to the laboratory were used in this study. Haloperidol, clozapine, aripiprazole, serotonin, noradrenaline, ATP and KCl were dissolved in 0.9% physiological saline. The mice were randomly divided into experimental groups as follows: saline; haloperidol 0.125 mg/kg; haloperidol 0.25 mg/kg; clozapine 1.25 mg/kg; clozapine 2.5 mg/kg; aripiprazole 3 mg/kg; aripiprazole 6 mg/kg. Mice were treated by ip injection of drugs during 21 days. Mice receiving only the vehicle ip (0.9% saline) during 21 days served as control group (n = 7). Each experimental group consisted of 7 mice. After 21 days of treatment, epididymal and prostatic portions of vas deferens were surgically dissected free and immersed in 20-mL organ baths containing Krebs’ solution. The effects of chronic treatment with haloperidol (0.125 and 0.25 mg/kg), clozapine(1.25 and 2.5 mg/kg) and aripiprazole (3 and 6 mg/kg) were investigated on serotonin [10 (−8) to 10 (−4) M], noradrenaline [10 (−8) to 10 (−4) M], ATP [10 (−8) to 10 (−4) M] and 80 mM KCl-induced contractile responses in the epididymal and prostatic portions of mice isolated vas deferens strips. Statistical comparison between the groups was performed using ANOVA supported by Dunnett’s post hoc test. Serotonin-induced contractile responses were significantly increased in the epididymal and prostatic portions of the vas deferens obtained from the haloperidol-treated group and clozapine-treated group. However, aripiprazole treatment had no effect on serotonin responses in both epididymal and prostatic portions of mice vas deferens. On the other hand, haloperidol and clozapine treatments significantly inhibited both noradrenaline and ATP-induced contractions of the prostatic and epididymal portions of the mice vas deferens, but had no effect on KCl-induced contractions of the vas deferens in both portions. There were no significant differences in KCl-induced contractile responses among the groups. These results revealed that induced contractions of vas deferens were affected after chronic treatment with haloperidol and clozapine but not aripiprazole. Serotonergic, noradrenergic and purinergic receptors may, at least in part, contribute to changes in vas deferens contractions in mice with chronic treatment of haloperidol and clozapine but not aripiprazole.

The role of phosphodiesterase (PDE) inhibitors in central nervous system has been investigated and shown to stimulate neuronal functions and increase neurogenesis in Alzheimer patients. The aim of this study is to investigate effect of PDE5 inhibitor zaprinast and PDE4 inhibitor rolipram on visual memory in novel object recognition (NOR) test, on olfactory memory in social transmission of food preference (STFP) test, and also on locomotion and anxiety in open field test in naive mice. Male Balb-c mice were treated intraperitoneally (i.p.) with zaprinast (3 and 10 mg/kg), rolipram (0.05 and 0.1 mg/kg), or physiological saline. Zaprinast (10 mg/kg) significantly increased cued/non-cued food eaten compared to control group, while rolipram had a partial effect on retention trial of STFP test. Zaprinast (10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) significantly increased ratio index (RI) compared to control group in retention trial of NOR test. There was no significant effect of zaprinast and rolipram on total distance moved, speed, and center zone duration in open field test. Results of this study revealed that both zaprinast and rolipram enhanced visual memory in NOR test, however zaprinast exerted a significant memory-enhancing effect compared to rolipram in STFP test in mice.