Clozapine Increases Nestin Concentration in the Adult Male Rat Hippocampus: A Preliminary Study

Patients with schizophrenia, and rodent models of the disease, both exhibit suppressed neurogenesis, with antipsychotics possibly enhancing neurogenesis in pre-clinical models. Nestin, a cytoskeletal protein, is implicated in neuronal differentiation and adult neurogenesis. We hy-pothesized that schizophrenia pathogenesis involves nestin downregulation; however, few studies have related nestin to schizophrenia. We assessed nestin protein concentration, prepulse inhibition (PPI), and social interaction in the MK-801 model of schizophrenia, with or without antipsychotic (clozapine) treatment. Adult male Sprague–Dawley rats were intraperitoneally administered saline or MK-801 (0.1 mg/kg) to produce a schizophrenia-like phenotype, with concomitant subcutaneous injections of vehicle or clozapine (5 mg/kg). PPI was assessed on days 1, 8, and 15, and social interaction was assessed on day 4. Hippocampus tissue samples were dissected for Western blotting of nestin concentration. MK-801 alone did not alter nestin concentration, while clozapine alone enhanced hippocampal nestin concentration; this effect was not apparent in animals with MK-801 and clozapine co-administration. MK-801 also produced schizophrenia-like PPI disruptions, some of which were reversed by clozapine. Social interaction deficits were not detected in this model. This is the first report of clozapine-induced enhancements of hippocampal nestin concentration that might be mediated by NMDA receptors. Future studies will explore the impact of neurodevelopmental nestin concentration on symptom onset and antipsychotic treatment

Central adenosinergic system and its clinical importance

Adenosine is a neuromodulator widely distributed throughout thebody. Since it is continuously synthesized, it can be concluded thatthere is a basal adenosinergic tonus, which has inhibitory effects ingeneral. All of the three adenosine receptors are G-protein coupled.While A1and A3receptor subtypes inhibit adenylate cyclase, A2subtypes activates it. A1and A2Areceptor subtypes, which bindadenosine with high affinity, are responsible for the basaladenosinergic tonus in physiological conditions. The most widelydistributed subtype, A1, is concentrated particularly in cerebral cortex,cerebellum and hippocampus. Adenosine has intense interactionswith other receptor systems. There are antagonistic interactionsbetween A1 dopamine D1and between A2and D2receptors.Adenosine is implicated in physiological processes such as initiationand maintenance of sleep, modulation of arousal, and control ofcerebral blood flow in response to energy demand of the brain.Adenosine is also implicated in cell-protection in pathologicalconditions like hypoxia and ischemia. Adenosine might be importantin the pathophysiology of anxiety, epilepsy, depression,schizophrenia, Parkinson’s disease, and addiction. The currentliterature about the central adenosinergic system is reviewe

GATA ASKERİ TIP FAKÜLTESİ’NDE GERÇEKLEŞTİRİLEN MADDE BAĞIMLILIĞI KONULU PANELİ DİNLEMEYE GELENLERDE BAĞIMLILIK YAPICI MADDE KULLANIMININ ANKET YÖNTEMİ İLE SORGULANMASI

Amaç: Madde bağımlılığı özellikle gelişmekte olan ülkelerde giderek artmakta olan bir sorundur. 1998 yılında Gülhane Askeri Tıp Akademisi (GATA) Askeri Tıp Fakültesi’nde düzenlenen “madde bağımlılığı” konulu panelde, bir anketle katılımcıların madde kullanım durumu ve konuyla ilgili görüşlerinin sorgulanması ve sonuçlarının değerlendirilmesi amaçlanmıştır. Yöntem: Düzenlenen paneli dinlemeye gelen katılımcılara hazırladığımız anket formlarından dağıtılarak katılımcılar hakkında genel bilgiler, bağımlılık yapıcı maddeleri kullanma durumları ve madde bağımlılığı hakkında düşünceleri sorgulandı. Dağıtılan 362 formdan 344 tanesi (%95) değerlendirmeye alındı. Bulgular: Değerlendirme sonucunda katılımcılar arasında sigara kullanımı %39, alkol kullanımı %40, bunların dışındaki illegal maddeleri kullanım oranı ise %2.3 olarak saptanmıştır. Sadece sigara veya alkol kullananlarda başka bir maddeyi kullanım eğilimi artmaktadır. Sigaraya başlama yaşı erkeklerde ortalama 15.7, kadınlarda 18.12; alkole başlama yaşı erkeklerde 17.0, kadınlarda 19.8 bulunmuştur. Katılımcıların %71’i madde bağımlılığının ciddi bir sorun olduğunun farkındadır. Mücadele konusunda ise büyük bir kesim (%87) aile ve toplumun bilinçlendirilmesi gerektiğini düşünmektedir. Sonuç: Katılımcıların sigara ve alkol kullanım oranının oldukça yüksek olduğu bulunmuştur. Maddelerin birlikte kullanımının daha yaygın olduğu ve madde kullanmaya başlamada arkadaş çevresinin etkili olduğu saptanmıştır. Tüm topluma yayılmış daha geniş çaplı epidemiolojik araştırmalar yapılması bağımlılık ile mücadelede daha etkin taktikler geliştirilmesine yardımcı olacaktır

Mirtazapine does not affect pentylenetetrazole- and maximal electroconvulsive shock-induced seizures in mice

Mirtazapine is an antidepressant exhibiting both noradrenergic and serotonergic activity. We have investigated the effects of mirtazapine on pentylenetetrazole (PTZ)- and maximal electroconvulsive shock (MES)-induced seizures in mice. Mirtazapine (1.25-20 mg/kg) or saline was administered, and locomotor activity was evaluated for 30 min. One hour after administration of mirtazapine (1.25-5 mg/kg) or saline, PTZ (80 mg/kg) was injected intraperitoneally into the mice. Immediately afterward, times of onset of the first myoclonic jerk (FMJ), generalized clonic seizures (GCS), and tonic extension (TE) were recorded. In the MES groups, we used the MES protocol to induce convulsions characterized by tonic hindlimb extension. Similarly, I h after mirtazapine or saline administration, an electroshock was evoked by ear-clip electrodes to induce convulsion. Mirtazapine, at 10 and 20 mg/kg, depressed locomotor activity. Doses of 1.255 mg/kg had no significant effect on the time of onset of FNIJ, GCS, or TE induced by PTZ; on the duration of GCS and TE1- or on the latency to reinstatement of the righting reflex after MES administration. Our results suggest that mirtazapine neither aggravates nor alleviates PTZ- or MES-induced seizures in mice. (c) 2007 Elsevier Inc. All rights reserved.Mirtazapine is an antidepressant exhibiting both noradrenergic and serotonergic activity. We have investigated the effects of mirtazapineon pentylenetetrazole (PTZ)- and maximal electroconvulsive shock (MES)-induced seizures in mice. Mirtazapine (1.25–20 mg/kg) orsaline was administered, and locomotor activity was evaluated for 30 min. One hour after administration of mirtazapine (1.25–5 mg/kg)or saline, PTZ (80 mg/kg) was injected intraperitoneally into the mice. Immediately afterward, times of onset of the first myoclonic jerk(FMJ), generalized clonic seizures (GCS), and tonic extension (TE) were recorded. In the MES groups, we used the MES protocol toinduce convulsions characterized by tonic hindlimb extension. Similarly, 1 h after mirtazapine or saline administration, an electroshockwas evoked by ear-clip electrodes to induce convulsion. Mirtazapine, at 10 and 20 mg/kg, depressed locomotor activity. Doses of 1.25–5 mg/kg had no significant effect on the time of onset of FMJ, GCS, or TE induced by PTZ; on the duration of GCS and TE; or on thelatency to reinstatement of the righting reflex after MES administration. Our results suggest that mirtazapine neither aggravates nor alleviatesPTZ- or MES-induced seizures in mice. 2007 Elsevier Inc. All rights reserved

Social interaction of rats is related with baseline prepulse inhibition level.

The symptoms of schizophrenia are evaluated in three general categories: positive, negative and cognitivesymptoms. Disruption of prepulse inhibition (PPI) of the acoustic startle reflex is commonly used to modelpositive and cognitive symptoms in experimental animals. On the other hand, deficient social interaction(SI) is a common model of negative symptoms. Here we tested whether PPI provides information aboutnegative symptoms by using a SI test. Baseline PPI and its relation with anxiety-like behavior were alsoexamined with elevated plus maze (EPM) test. In the first experiment, baseline PPI levels of 30 Wistarrats were measured and animals with the highest 1/3 and the lowest 1/3 of PPI scores were respectivelyassigned in high-inhibitory (HI) and low-inhibitory (LI) groups. Subsequently, rats in the HI and LI groupswere paired with animals from the same group and tested for SI. In the second experiment, another batchof animals was assigned to HI and LI groups and they were investigated in the EPM test. The results demon-strate a significant difference between the PPI values of HI and LI groups. Both the SI time and the movingdistance of LI rats were significantly lower, and the average distance between rat pairs was significantlylonger than HI rats. In the EPM test LI and HI rats showed similar levels of anxiety-like behaviors, howeverour results imply that performance of the rats in the SI test is related to baseline PPI levels. Thus PPI testcan provide predictive information about the outcome of animal models for negative symptoms in rats

Effects of escitalopram on ethanol withdrawal syndrome in rats

The present study was designed to investigate the effects of escitalopram, a selective serotonin reuptake inhibitor, on ethanol withdrawal syndrome in rats. Adult male Wistar rats (266-278 g) were subjects. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair fed with an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. Escitalopram, (2.5, 5 and 10 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After the second and sixth hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behavior, wet dog shakes, tremors and audiogenic seizures were recorded or rated. A second series of injections was given 30 min before sixth hour of withdrawal test. Effects of escitalopram on the locomotor activities of the naive (no ethanol-dependent) rats were also evaluated. Escitalopram (5 mg/kg) reduced the increased stereotyped behaviors at the sixth hour of ethanol withdrawal. It inhibited tremors at the second hour of ethanol withdrawal at doses of 5 and 10 mg/kg. Escitalopram (2.5 and 5 mg/kg) also produced some significant attenuations in the incidence of wet dog shakes at the second and sixth hours of the observation period. It was found ineffective on locomotor hyperactivity, agitation and audiogenic seizures. Escitalopram (2.5 and 5 mg/kg) did not cause any significant effect on locomotor activities of the naive rats. Our results suggest that acute escitalopram treatment has some limited beneficial effects on ethanol withdrawal syndrome in rats. (c) 2006 Elsevier Inc. All rights reserved

Effects of olanzapine on ethanol withdrawal syndrome in rats

The present study was designed to investigate the effects of olanzapine, a serotonin-dopamine antagonistic atypical antipsychotic agent, on ethanol withdrawal syndrome in rats. Adult male Wistar rats were subjects. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair fed with an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. After 2nd, 4th and 6th h of ethanol withdrawal, rats were observed for 5 min, afterwards withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behavior, tremor, wet dog shakes, abnormal posture and abnormal gait were recorded or rated. Olanzapine (0.5, 1 and 2 mg/kg) and saline were injected to the rats intraperitoneally 30 min before ethanol withdrawal assessment. A second series of injections was also given 30 rain before the 6th-h-observation, and subjects were then tested for audiogenic seizures. Olanzapine (2 mg/kg) produced significant inhibitory effects on stereotyped behaviors and wet dog shakes at the 6th h of ethanol withdrawal. Contrary, the same dose caused some increases in the intensity of posture and gait impairments at the 2nd h of ethanol withdrawal. In addition, that dose was found to be ineffective on agitation, tremor, tail stiffness and audiogenic seizures. Our results suggest that acute olanzapine treatment has beneficial effects on stereotyped behavior and wet dog shakes, but it also has some adverse effects on posture and gait during ethanol withdrawal in rats. Overall, olanzapine does not seem to be an adequate and suitable drug in controlling of ethanol withdrawal syndrome. (c) 2007 Elsevier B.V. All rights reserved

Audiogenic Seizures Potentiate Hippocampal Neuronal Loss in Ethanol-Dependent Rats

Objective: Audiogenic seizure (AS) susceptibility is observed following withdrawal from chronic ethanol treatment in rodents. This is the first study to investigate and compare the effects of ethanol withdrawal on the hippocampal formation in AS appeared and nonappeared animals