ABSTRACT
Nitric oxide plays a role in a series of neurobiological functions, underlying behaviour and memory. The functional role of nNOS derived nitric oxide in cognitive functions is elusive. The present study was designed to investigate the effect of specific neuronal nitric oxide synthase inhibitor, 7-nitroindazole, against intracerebroventricular streptozotocin-induced cognitive impairment in rats. Learning and memory behaviour was assessed using Morris water maze and elevated plus maze. 7-nitroindazole (25 mg/kg, ip) was administered as prophylactically (30 min before intracerebroventricular streptozotocin injection on day 1) and therapeutically (30 min before the assessment of memory by Morris water maze on day 15). Intracerebroventricular streptozotocin produced significant cognitive deficits coupled with alterations in biochemical indices.These behavioural and biochemical changes were significantly prevented by prophylactic treatment of 7-nitroindazole. However, therapeutic intervention of 7-nitroindazole did not show any significant reversal. The results suggests that 7-nitroindazole can be effective in the protection of dementiainduced by intracerebroventricular streptozotocin only when given prophylactically but not therapeutically.
Subject(s)
Alzheimer Disease/chemically induced , Alzheimer Disease/enzymology , Alzheimer Disease/pathology , Animals , Cognition Disorders/chemically induced , Cognition Disorders/enzymology , Cognition Disorders/pathology , Enzyme Inhibitors/administration & dosage , Humans , Indazoles/administration & dosage , Male , Maze Learning/drug effects , Maze Learning/physiology , Neurons/metabolism , Neurons/pathology , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/antagonists & inhibitors , Nitric Oxide Synthase Type I/metabolism , Rats , Streptozocin/toxicityABSTRACT
The involvement of adenosinergic pathway in the anti-nociceptive effect of duloxetine, a balanced 5-HT/NE reuptake inhibitor, was evaluated in streptozotocin induced diabetic male albino mice of Laca strain. After four weeks of single injection of streptozotocin (200 mg/kg, ip), mice were tested in the tail immersion and hot-plate assays. Cerebral adenosine levels were measured by high-performance liquid chromatography (HPLC/PDA detector). Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose, decreased body weights and reduced cerebral adenosine levels. Administration of duloxetine (5, 10 and 20 mg/kg, ip) to diabetic mice produced dose-dependent anti-nociceptive effect in both tail-immersion and hot-plate assays. Adenosine levels were also significantly and dose-dependently increased by different doses of duloxetine. The results demonstrated the involvement of adenosinergic pathway in duloxetine mediated anti-hyperalgesia in diabetic neuropathic pain.
Subject(s)
Adenosine/metabolism , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Diabetes Mellitus, Experimental/complications , Diabetic Neuropathies/drug therapy , Dose-Response Relationship, Drug , Hot Temperature , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Male , Mice , Mice, Inbred Strains , Pain Measurement , Pain Threshold/drug effects , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/pharmacology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Streptozocin , Thiophenes/administration & dosage , Thiophenes/pharmacology , Thiophenes/therapeutic use , TouchABSTRACT
Peripheral neuropathy is one of the common complications of diabetes mellitus. It is frequently associated with debilitating pain. The present study was designed to investigate effect of Lycopene, a carotenoid found in tomatoes, on hyperalgesia and cold allodynia in streptozotocin (STZ) induced diabetic rats. After 4-weeks of STZ injection, diabetic mice exhibited a significant thermal hyperalgesia cold allodynia, hyperglycemia and loss of body weights as compared with control rats. Chronic treatment of lycopene for 4 weeks significantly attenuated the cold allodynia and thermal hyperalgesia. The results emphasize the role of antioxidant such as lycopene as an adjuvant therapy in the treatment of diabetic neuropathy.