Abscisic acid interplays with PPARγ receptors and ameliorates diabetes-induced cognitive deficits in rats

Objective: This study intended to evaluate if central administration of abscisic acid (ABA) alone or in combination with GW9662, a peroxisome proliferator–activated receptor γ (PPAR-γ) antagonist, could modulate learning and memory as well as hippocampal synaptic plasticity in a rat model of streptozotocin (STZ)–induced diabetes. Materials and Methods: Intraperitoneal injection of STZ (65 mg/kg) was used to induce diabetes. Diabetic rats were than treated with intracerebroventricular (i.c.v.) administration of ABA (10, 15 and 20 µg/rat), GW9662 (3 µg/rat) or GW9662 (3 µg/rat) plus ABA (20 µg/rat).Animals’ spatial and passive avoidance learning and memory performances were assessed by Morris water maze (MWM) and shuttle box tasks, respectively. Further, in vivo electrophysiological field recordings were assessed in the CA1 region. Results: STZ diabetic rats showed diminished learning and memory in both MWM and shuttle box tasks.  The STZ-induced memory deficits were attenuated by central infusion of ABA (10 and 20 µg/rat). Besides, STZ injection impaired long-term potentiation induction in CA1 neurons that was attenuated by ABA at 20 μg/rat. Central administration of GW9662 (3 µg/rat) alone did not modify STZ-induced spatial and passive avoidance learning and memory performances of rats. Further, GW9662 prevented ABA capacity to restore learning and memory in behavioral and electrophysiology trials. Conclusion: Altogether, ABA ameliorates cognitive deficits in rats via activation of PPAR-γ receptor in diabetic rats

A modification of a previous model for inflammatory tooth pain: Effects of different capsaicin and formalin concentrations and ibuprofen

BACKGROUND AND AIM: This study aimed to solve the problems faced with the previous model of inflammatory tooth pain in rats. METHODS: After cutting 2 mm of the distal extremities, the polyethylene crowns were placed on the mandibular incisors. In contrast to the original model, we used flow composite instead of wire in order to maximize the retention of crowns. Different concentrations of capsaicin (10, 25 and 100 mg/ml) and formalin were administrated into the cavities under the crowns. The algesic agent-induced behaviors were evaluated. RESULTS: The modified model had no liquid leakage. Furthermore, composite allowed the crowns to remain for a longer period of time. Capsaicin 25, 100 mg/ml and formalin applications induced significantly more painful stimulation compared with control groups (P < 0.001). These responses were significantly reduced by the administration of ibuprofen, 20 minutes prior to the capsaicin 100 mg/ml injection. CONCLUSIONS: This model seems to be adequate for long-term pain related experiments in which fluid leakage elimination is important. KEY WORDS: Odontalgia, Capsaicin, Formalin, Model, Ra

Research Paper: The Modulatory Role of Orexin 1 Receptor in CA1 on Orofacial Pain-induced Learning and Memory Deficits in Rats

Introduction: Cognitive impairment is commonly associated with pain. The modulatory role of orexin 1 receptor (OX1R) in pain pathways as well as learning and memory processes is reported in several studies. The current study was designed to investigate the possible role of CA1-hippocampal OX1R on spatial learning and memory of rats following capsaicin-induced orofacial pain. Methods: Orofacial pain was induced by subcutaneous intra lip injection of capsaicin (100 &mu;g). CA1 administration of orexin A and its selective antagonist (SB-334867-A) were performed 20 minutes prior to capsaicin injection. Learning and spatial memory performances were assessed by Morris Water Maze (MWM) task. Results: Capsaicin treated rats showed impairment in spatial learning and memory. In addition, pretreatment with orexin A (20 and 40 nM/rat) significantly attenuated learning and memory impairment in capsaicin-treated rats. Conversely, blockage of OX1R via SB-334867-A (40 and 80 nM/rat) significantly exaggerated learning and memory loss in capsaicin-treated rats.&nbsp; Conclusion: The obtained results indicated that CA1 OX1R may be involved in modulation of capsaicin &ndash;induced spatial learning and memory impairment

The ability of orexin-A to modify pain-induced cyclooxygenase-2 and brain-derived neurotrophic factor expression is associated with its ability to inhibit capsaicin-induced pulpal nociception in rats

Background: The rostral ventromedial medulla (RVM) is a critical region for the management of nociception. The RVM is also involved in learning and memory processes due to its relationship with the hippocampus. The purpose of the present study was to investigate the molecular mechanisms behind orexin-A signaling in the RVM and hippocampus’s effects on capsaicin-induced pulpal nociception and cognitive impairments in rats. Methods: Capsaicin (100 g) was applied intradentally to male Wistar rats to induce inflammatory pulpal nociception. Orexin-A and an orexin-1 receptor antagonist (SB-334867) were then microinjected into the RVM. Immunoblotting and immunofluorescence staining were used to check the levels of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) in the RVM and hippocampus. Results: Interdental capsaicin treatment resulted in nociceptive responses as well as a reduction in spatial learning and memory. Additionally, it resulted in decreased BDNF and increased COX-2 expression levels. Orexin-A administration (50 pmol/1 μL/rat) could reverse such molecular changes. SB-334867 microinjection (80 nM/1 μL/rat) suppressed orexin’s effects. Conclusions: Orexin-A signaling in the RVM and hippocampus modulates capsaicin-induced pulpal nociception in male rats by increasing BDNF expression and decreasin COX-2 ex ression

Involvement of Mu Opioid Receptor Signaling in The Protective Effect of Opioid against 6-Hydroxydopamine-Induced SH-SY5Y Human Neuroblastoma Cells Apoptosis

Introduction: The neuroprotective role of opioid morphine against 6-hydroxydopamineinduced cell death has been demonstrated. However, the exact mechanism(s) underlying such neuroprotection, especially the role of subtype receptors, has not yet been fully clarified. Methods: Here, we investigated the effects of different opioid agonists on 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cell line as an in vitro model of Parkinson’s disease. Cell damage was induced by 150 μM 6-OHDA and the cells viability was examined by MTT assay. Intracellular calcium, reactive oxygen species and mitochondrial membrane potential were assessed by fluorescence spectrophotometry method. Immunoblot technique was used to evaluate cytochrome-c and activated caspase-3 as biochemical markers of apoptosis induction. Results: The data showed that 6-OHDA caused significant cell damage, loss of mitochondrial membrane potential and increase in intracellular reactive oxygen species and calcium levels as well as activated caspase-3 and cytochrome-c release. Incubation of SH-SY5Y cells with μ-opioid agonists, morphine and DAMGO, but not with δ-opioid agonist, DADLE, elicited protective effect and reduced biochemical markers of cell damage and death. Discussion: The results suggest that μ-opioid receptors signaling participate in the opioid neuroprotective effects against 6-OHDA-induced neurotoxicity

The effect of CA1 administration of orexin-A on hippocampal expression of COX-2 and BDNF in a rat model of orofacial pain

ABSTRACT The neuropeptide orexin-A and its receptors are widely distributed in both hippocampal circuitry and pain transmission pathways. Objective: Involvement of the CA1 orexin 1 receptor (OX1R) on the modulation of orofacial pain and pain-induced changes in hippocampal expression of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) was investigated. Methods: Orofacial pain was induced by an intra-lip injection of capsaicin (100 μg). Reverse transcription polymerase chain reaction and immunoblot analysis were used to indicate changes in hippocampal BDNF and COX-2 expression, respectively. Results: Capsaicin induces a significant pain response, which is not affected by either orexin-A or SB-334867-A, an OX1R antagonist. However, an increased expression of COX-2 and decreased expression of BDNF was observed in the hippocampus of animals that received capsaicin or SB-334867-A (80 nM) plus capsaicin. Meanwhile, orexin-A (40 pM) attenuated the effects of capsaicin on the expression of COX-2 and BDNF. Conclusions: CA1 OX1R activation moderates capsaicin-induced neuronal inflammation and neurotrophic deficiency

A convenient one-pot synthesis and anxietic activity of 3-cyano-2(1H)-iminopyridines and halogen derivatives of benzo[h]chromenes

A general and easy method for the synthesis of 4,6-disubstituted-3-cyano-2(1H)-iminopyridine or 3-amino-6-chloro-1-aryl-1H-benzo[h]chromen-2-yl cyanide derivatives in the presence of high surface area MgO as a highly effective heterogeneous base catalyst is described. These compounds were synthesized using one-pot multicomponent reactions of the properly substituted acetophenone, appropriate aldehyde, ammonium acetate and malononitrile or three component reactions of 4-chloro-2-naphthol, aldehydes and malononitrile, respectively, in DMF. The compound of 7c was evaluated for its anxiolytic activities