No abstract

The prototypic cannabinoid CB1 antagonist SR 141716A is one important pharmacologic tool for examining CB1 receptors that mediate the behavioral and physiologic effects of delta9-tetrahydrocannabinol (delta9-THC). This study examined the effects of SR 141716A on the rate-decreasing, hypothermic and discriminative stimulus effects of delta9-THC in rhesus monkeys. In monkeys (n=4) responding under a multiple fixed ratio (FR-10:FR-10) schedule of food presentation and stimulus-shock termination, the potency of i.m. delta9-THC to decrease responding in the food component (ED50=0.64 mg/kg) was threefold greater than its potency in the stimulus-shock termination component (ED50=2.14 mg/kg). In the same monkeys, hypothermia was induced by delta9-THC at a dose (e.g. 0.32 mg/kg) that did not alter responding in either schedule component; the maximum decrease was 2.1 degrees C at a dose of 3.2 mg/kg. A dose of 0.32 mg/kg of SR 141716A, significantly attenuated delta9-THC-induced hypothermia without attenuating the rate-decreasing effects of delta9-THC in either component of the multiple schedule. The largest dose of i.m. SR 141716A that was studied, 1.0 mg/kg, significantly decreased rectal temperature and responding in the food component but did not significantly decrease responding in the stimulus-shock termination component of the multiple schedule. In a separate group of monkeys (n=3) that discriminated i.v. delta9-THC (0.1 mg/kg) while responding under an FR-5 schedule of stimulus-shock termination, SR 141716A (0.32 and 1 mg/kg) significantly increased the ED50 of the delta9-THC by 2.3- and 3.7-fold, respectively. Collectively, these results demonstrate that the behavioral effects of delta9-THC are not equally attenuated by SR 141716A.

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is involved in modulation of diverse physiological processes. The role of this receptor in epilepsy has not been studied well. Therefore, we investigated the role of central TRPV1 receptors on the development of pentylenetetrazole (PTZ) and amygdala-induced kindling in rats. Male Wistar rats received subconvulsive dose of PTZ intraperitoneally, every other day. TRPV1 receptor agonist, OLDA and its antagonist, AMG-9810 were injected intracerebroventricularly 30 min prior to PTZ administration. In electrical kindling, stimulating and recording electrodes were implanted in the right amygdala of male rats. After kindling, the effect of TRPV1 receptor agonist or antagonist on afterdischarge duration (ADD), latency to the onset of bilateral forelimb clonuses (S4L) and duration of loss of equilibrium (stage 5 seizures, S5D) were measured. The results demonstrated that, OLDA at the doses of 0.01, 0.1 and 1 μg/rat, significantly accelerated the incidence of all seizure stages, increased S5D and decreased S4L in the PTZ model of kindling. Also, in amygdala kindling, S5D and ADD were significantly reduced following the administration of AMG-9810. In contrast, OLDA significantly aggravated the indices of seizure in both models of epileptic seizure. This study demonstrated that central TRPV1 receptors may be involved in the development of electrical and PTZ-induced kindling.

No abstract

Objective: Inflammation plays a significant role in the development of ischemic stroke. CXC chemokines play pleiotropic roles in prolonged leukocyte locomotion, astrocyte migration/activation, and neural attachment/sprouting in response to focal stroke. In this study, we aimed to explore the changes in serum levels of three chemokines, C-X-C motif chemokine ligand 1 (CXCL1), C-X-C motif chemokine ligand 9 (CXCL9), and C-X-C motif chemokine ligand 10 (CXCL10), in ischemic stroke patients at the time of admission and before discharge from the hospital ward. Materials and Methods:In this study, we recruited 43 unrelated ischemic stroke patients using an easy convenience method or accidental sampling which is a type of non-probability sampling that involves the sample being drawn from that part of the population that is close to hand. We also enrolled 50 genetically unrelated healthy controls showing no history of neurologic, cardiovascular, or inflammatory diseases. Serum levels of the considered chemokines were measured by enzyme-linked immunosorbent assay (ELISA) in patients and healthy controls.Results: No significant difference was observed in ischemic stroke patients following hospitalization and prior discharging from the hospital; however, there was a significant difference in serum levels of CXCL9 and CXCL10 between patients and healthy controls. We also found that the level of the chemokine was not related to gender or medical therapy. It appears that CXCL9 and CXCL10 are more predisposing factors and play a direct role in stroke considering that they were higher in patients than in healthy controls. Conclusion:We believe that this study might be used as a basis for further studies on more effective medication regimens to prevent the onset and subsequent complications of stroke. However, these mediators are useful diagnostic and prognostic tools rather than therapeutic tools.Keywords: Chemokine, ischemia, stroke ÖZ Amaç: Enflamasyon iskemik inme gelişiminde önemli bir rol oynar. CXC kemokinlerinin fokal inmeye yanıt olarak gelişen nöral bağlanma/filizlenme, astrosit migrasyon/aktivasyon ve uzamış lökosit lokomosyonunda pleiotropic etkileri vardır. Bu çalışmada iskemik inmeli hastalarda, C-X-C motif kemokin ligand 10 (CXCL10), C-X-C motif kemokin ligand 1 (CXCL1) ve C-X-C motif kemokin ligand 9'u (CXCL9) içeren üç kemokinin serum düzeyindeki değişikliklerinin hastaneye kabul ve taburculuk sırasında araştırılması amaçlanmıştır.Gereç ve Yöntem: Bu çalışmada, kolay uygunluk yöntemi kullanılarak birbiriyle ilişkisi olmayan 43 iskemik inmeli hasta incelendi. Ayrıca herhangi bir nörolojik, kardiyovasküler veya inflamatuvar hastalık öyküsü olmayan, genetik olarak birbiriyle bağlantısız 50 sağlıklı denek de çalışmaya dahil edildi. Hastalarda ve sağlıklı kontrollerde kemokinlerin serum düzeyleri enzime bağlı bağışıklık deneyi (ALISA) ile ölçüldü.Bulgular: Mevcut çalışmada, iskemik inme geçirdiği için hastaneye yatırılan ve taburcu edilen hastalarda anlamlı bir farklılık izlenmedi. Ancak, hastalar ve sağlıklı...