Naresh Khanna

Antagonism of stimulation-produced analgesia by naloxone and N-methyl-D-aspartate: role of opioid and N-methyl-D-aspartate receptors.

The present study aims to investigate the influence of electrical stimulation of periaqueductal gray (PAG) following peripheral nerve injury and its modulation by naloxone and N-methyl-D-aspartate (NMDA). Chronic neuropathic pain was induced by chronic constriction injury of the sciatic nerve, and subsequently a cannula was implanted in the PAG area for the purpose of electrical stimulation and intra-PAG drug administration. Intra-PAG administration of morphine, ketamine, and their combination were found to elicit antinociceptive response on hot-plate test. Electrical stimulation of PAG was also observed to demonstrate decreased pain response on hot-plate test, and this effect was reversed by the administration of naloxone, NMDA, and their combination, when injected into the PAG area. These findings suggest that apart from the opioid receptors, probably NMDA receptors also have a role to play in stimulation-produced analgesia.

The effect of high-fat diet-induced obesity on cardiovascular toxicity in wistar albino rats

The consumption of a high-fat diet (HFD) is considered a risk factor for obesity development. Nonetheless, a causal role of dietary fat has never been documented, because of inadequate animal models. In our study, one group of rats was fed with standard rat diet, while other group of rats fed with high-fat diet for 4 weeks. After 4 weeks of feeding, the hemodynamic parameters in the rats fed with HFD were significantly increased as compared with control rats. Rats fed with HFD had elevated levels of serum lipids, insulin, leptin, glucose and apolipoprotein B. Lipid peroxides and caspase-3 levels were increased while serum apolipoprotein A1 and antioxidant enzymes levels in heart tissues were decreased in HFD-induced obesity in rats as compared to normal healthy control rats fed on standard rat pellet diet. This model of diet-induced obesity will be a useful tool for studying the mechanisms by which dietary fat induces the obesity in humans.

Melatonin attenuates cognitive dysfunction and reduces neural oxidative stress induced by phosphamidon

Melatonin is an important modulator of nervous system functioning and important neural antioxidant. Organophosphate pesticides like phosphamidon (PHOS) have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of PHOS on cognitive function by melatonin (MEL). Cognitive function was assessed using step‐down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP‐SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the PHOS (1.74 mg/kg/day; p.o.)‐treated group at weeks 6 and 8 as compared to the control group. Two‐week treatment with MEL (5 mg/kg/day; i.p.) antagonized the effect of PHOS on SDL as well as TL. PHOS alone produced a significant increase in the brain MDA levels and decrease in the brain NP‐SH levels. Treatment with MEL attenuated the effect of PHOS on oxidative stress. Together the results showed that MEL attenuated the cognitive dysfunction and decreased oxidative stress induced by PHOS in the brain.

Interaction of morphine and potassium channel openers on experimental models of pain in mice

Combination of opioid and potassium channel openers holds immense potential for the treatment for most acute and chronic pain. Therefore, the study was performed to assess the interaction between morphine and K+‐channel openers. Swiss albino mice of either sex weighing between 25 and 30 g were used for the study. The study assesses the interaction between morphine and K+‐channel openers (cromakalim, diazoxide and minoxidil), when administered intraperitoneally, using formalin and tail‐flick tests in mice. Both morphine and K+‐channel openers produced significant antinociception at higher doses in both the behavioral tests. Lower doses of morphine and K+‐channel openers had no significant effect on tail‐flick latency, while the same drugs had significant antinociceptive effect on formalin test. The combination of lower doses of morphine and K+‐openers was observed to have significant antinociceptive effect in both the behavioral tests. Administration of naloxone prior to morphine or K+‐channel openers antagonized the analgesic effect of morphine but not of K+‐channel openers, whereas prior administration of glibenclamide antagonized the effect of both morphine and K+‐channel openers. The study, therefore, suggests that the common site of action of morphine and K+‐channel openers is at the levels of K+‐channels rather than at the level of receptors. However, such interaction depends on the differential sensitivity to different pain stimulus.

Protective effect of melatonin on propoxur-induced impairment of memory and oxidative stress in rats

Propoxur (a carbamate pesticide) has been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. This study was designed to explore the modulation of the effects of propoxur over cognitive function by melatonin (MEL). Cognitive function was assessed using step‐down latency (SDL) on a passive avoidance apparatus, and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining brain malondialdehyde (MDA) and reduced glutathione (GSH) levels and catalase (CAT) activity. A significant reduction in SDL and prolongation of TL was observed for the propoxur (10 mg/kg/d; p.o.) treated group at weeks 6 and 7 when compared with control. One week treatment with MEL (50 mg/kg/d; i.p.) antagonized the effect of propoxur on SDL, as well as TL. Propoxur produced a statistically significant increase in the brain MDA levels and decrease in the brain GSH levels and CAT activity. Treatment with MEL attenuated the effect of propoxur on oxidative stress. The results of the present study thus show that MEL has the potential to attenuate cognitive dysfunction and oxidative stress induced by toxicants like propoxur in the brain.

Effect of piracetam and vitamin E on phosphamidon-induced impairment of memory and oxidative stress in rats

Organophosphate pesticides, such as phosphamidon (PHOS), have been shown to adversely affect memory and induce oxidative stress after both acute and chronic exposure. The present study was therefore designed to investigate the effects of piracetam (PIR) and vitamin E on PHOS-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of malondialdehyde (MDA) and nonprotein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and a prolongation of TL in the PHOS (1.74 mg/kg/day per oral; p.o.)-treated group at weeks 6 and 8, as compared to the control group. Administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) for 2 weeks antagonized the effect of PHOS on SDL as well as TL. PHOS per se produced a significant increase in brain MDA levels and a decrease in brain NP-SH levels, whereas administration of PIR (600 mg/kg/day p.o.) or vitamin E (125 mg/kg/day p.o.) attenuated these effects. Thus, the results of the study showed that both PIR and vitamin E attenuated the cognitive dysfunction and oxidative stress induced by PHOS in the rat brain.

Role of NMDA and opioid receptors in neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

Abstract Background: The efficacy of opioids in neuropathic pain is still controversial. Earlier studies have suggested that N-methyl-D-aspartate (NMDA) receptor binding can be affected by opioids and vice versa. The present study aims to explore the interactions between NMDA and opioid receptors using various combinations of drugs acting on these receptors. Methods: We used an animal model of sciatic nerve ligation to induce neuropathic pain, and a hot-plate test was used to assess pain response. Results: It was observed that NMDA and naloxone increased the pain response. Ketamine reduced the pain response, which was further reduced when ketamine was administered in combination with naloxone, but not with NMDA, thus highlighting the activity of the NMDA receptor system. In addition, morphine was also found to increase latency to hind-paw lick, which was further reduced when given in combination with naloxone. Furthermore, triple drug combinations using ketamine+morphine+naloxone and ketamine+NMDA+naloxone demonstrated some significant interactions at these receptors. Conclusions: Thus, our study establishes that neuropathic pain can probably be overcome using higher doses of opioids, and there exists some intimate relationships between NMDA and opioid systems that lead to pain modulation.

Effect of progesterone on phosphamidon-induced impairment of memory and oxidative stress in rats

Progesterone (a neurosteroid) is an important modulator of the nervous system functioning. Organophosphorus pesticides like phosphamidon have been shown to adversely affect memory and induce oxidative stress on both acute and chronic exposure. The present study was therefore designed to investigate the effects of progesterone (PROG) on phosphamidon-induced modulation of cognitive function and oxidative stress in rats. Cognitive function was assessed using step-down latency (SDL) on a passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in isolated homogenized whole brain samples. The results showed a significant reduction in SDL and prolongation of TL in the phosphamidon (1.74 mg/kg/d; p.o.) treated group at weeks 6 and 8 as compared to the control group. Two weeks treatment with PROG (15 mg/kg/d; i.p.) antagonized the effect of phosphamidon on SDL as well as TL. Phosphamidon alone produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. Treatment with PROG (15 mg/kg/d; i.p.) attenuated the effect of phosphamidon on oxidative stress. Together, the results showed that progesterone attenuated the cognitive dysfunction and increased oxidative stress induced by phosphamidon in the brain.

The effect of the essential oil of Eugenia caryophyllata in animal models of depression and locomotor activity

Abstract Objective The essential oil of Eugenia caryophyllata (clove oil; Family: Myrtaceae) is used in dental care as an antiseptic and analgesic. The present study investigates the effect of clove oil on animal models of depression and locomotion. Methods Clove oil was administered in doses of 0.025, 0.05, and 0.1 ml/kg/day, intraperitoneally (i.p.) for 3 weeks. The forced swim test (FST) and the tail suspension test (TST) were used to assess depression. To evaluate locomotor activity, the rota rod test and the photoactometer procedure were performed. Results In the FST, it was observed that the duration of immobility was significantly decreased (P < 0.01) in animals treated with clove oil (0.05 and 0.1 ml/kg); however, the clove oil dose of 0.025 ml/kg showed an insignificant increase in the immobile period. The TST demonstrated that pretreatment with clove oil decreases (P < 0.01) the immobile period significantly at all the three administered doses. Similarly, the photoactometer procedure showed increased locomotor activity at all the three doses, although significant (P < 0.05) only at 0.1 ml/kg. In addition, the rota rod test showed that animals treated with clove oil (0.1 ml/kg) enhanced muscle coordination as demonstrated by a significant increase (P < 0.05) in the latency to fall from the rota rod as compared to the control. However, the lowest administered dose (0.025 ml/kg, i.p.) decreased the latency to fall from the rota rod significantly (P < 0.05) compared to the control. Clove oil (0.05 ml/kg) also showed a decrease in the latency to fall from the rota rod although the result was not statistically significant. Discussion Thus, it can be concluded that pretreatment with clove oil decreases depression and enhances locomotor activity similar to that exhibited by psychostimulants.