Nardostachys jatamansi extract prevents chronic restraint stress-induced learning and memory deficits in a radial arm maze task.

Nardostachys jatamansi is traditionally used in alternative medicine for treatment of neuropsychiatric disorders. We investigated the potential of N. jatamansi extract (NJE) in protecting against chronic stress-induced impairments in spatial learning and memory. The rats were exposed to 21 days of chronic restraint stress and simultaneously received 100 mg or 200 mg/kg body weight of NJE following which acquisition and retention of hippocampus-dependent spatial memory were tested in a partially-baited eight arm radial maze. Animals treated with 200 mg/kg body weight NJE had learning curves comparable to control unstressed animals, made significantly more correct choices (38%, P < 0.001), and fewer reference memory errors (53%, P < 0.01) on the eighth day of training compared to untreated stressed animals as well as stressed animals which received vehicle or a lower dose (100 mg/kg) of NJE. NJE-treated animals also made significantly higher correct choices (31%, P < 0.001) than untreated animals in a retention test 10 days after the training period. We propose that NJE has a protective effect of stress-induced impairments in hippocampus-dependent learning and memory behavior in rats.

Clitoria ternatea root extract enhances acetylcholine content in rat hippocampus.

Treatment with 100 mg/kg of Clitoria ternatea aqueous root extract (CTR), for 30 days in neonatal and young adult age groups of rat, significantly increased acetylcholine (ACh) content in their hippocampi as compared to age matched controls. Increase in ACh content in their hippocampus may be the neurochemical basis for their improved learning and memory.

Effects of administration of nicorandil or bimakalim prior to and during ischemia or reperfusion on survival rate, ischemia/reperfusion-induced arrhythmias and infarct size in anesthetized rabbits.

We investigated the effects of administration of non-hypotensive doses of ATP-sensitive K+ channel (KATP) openers (nicorandil and bimakalim), and a specific mitochondrial KATP channel blocker (5-hydroxydecanoate) prior to and during coronary occlusion as well as prior to and during post-ischemic reperfusion on survival rate, ischemia-induced and reperfusion-induced arrhythmias and myocardial infarct size in anesthetized albino rabbits. The thorax was opened in the left fourth intercostal space and after pericardiotomy the heart was exposed. In Part I, occlusion of the left main coronary artery and hence, myocardial ischemia-induced arrhythmias were achieved by tightening a previously placed loose silk ligature for 30 min. In Part II, arrhythmias were induced by reperfusion following a 20-min ligation of the left main coronary artery. In Part I, early intravenous infusion of nicorandil (100 microg/kg bolus + 10 microg/kg per min) or bimakalim (3 microg/kg bolus + 0.1 microg/kg per min) just prior to and during ischemia increased survival rate (75% and 67% vs. 60% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. In Part II also, early intervention by intravenous infusion of nicorandil (100 microg/kg bolus + 10 microg/kg per min) or bimakalim (3 microg/kg bolus + 0.1 microg/kg per min) just before and during ischemia increased survival rate (86% and 75% vs. 55% in the control group), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. However, late intravenous administration of nicorandil or bimakalim at the onset and during reperfusion did not increase survival rate nor confer any antiarrhythmic or cardioprotective effects. The antiarrhythmic and cardioprotective effects of both nicorandil and bimakalim were abolished by pretreating the rabbits with 5-hydroxydecanoate (5 mg/kg, i.v. bolus), a selective mitochondrial KATP channel blocker. In conclusion, intervention by intravenous administration of nicorandil and bimakalim (through the activation of mitochondrial KATP channels), increased survival rate and exhibited antiarrhythmic and cardioprotective effects during coronary occlusion and reperfusion in anesthetized rabbits when administered prior to and during coronary occlusion.

Effects of nicorandil administration on survival rate and arrhythmias during reperfusion in anesthetized rabbits.

The aim was to study the effects of nicorandil (an ATP-sensitive K+ channel opener) and tolbutamide (an ATP-sensitive K+ channel blocker) on reperfusion-induced arrhythmias in pentobarbitone and ketamine anesthetized rabbits. Arrhythmias were induced by reperfusion for 20 min following a 15-min ligation of the left main coronary artery with a silk ligature. Rabbits were pretreated with nicorandil (0.47, 0.93 or 1.86 mg/kg i.v.) or tolbutamide (180 mg/kg i.p.) or vehicle (dimethylsulfoxide/saline) before the coronary artery occlusion. In the control group (n = 10), only 60% of the animals survived during reperfusion. Intravenous pretreatment with 0.47, 0.93 or 1.86 mg/kg of nicorandil increased the survival rate to 86% (n = 7), 75% (n = 8) and 86% (n = 7), respectively. Nicorandil pretreatment significantly decreased the incidence and duration of reperfusion-induced life-threatening arrhythmias and increased the number of animals that survived without developing any arrhythmia. Tolbutamide pretreatment was associated with a decreased survival rate of 50% (n = 12) and an increase in the incidence and duration of reperfusion-induced arrhythmias. Pretreatment with nicorandil may result in protection against reperfusion-induced arrhythmias and increased survival in anesthetized rabbits.

Clitoria ternatea (Linn) root extract treatment during growth spurt period enhances learning and memory in rats.

Neonatal rat pups (7 days old) were intubated with either 50 mg/kg body weight or 100 mg/kg body weight of aqueous root extract of Clitoria ternatea (CTR) for 30 days. These rats were then subjected to open field, two compartment passive avoidance and spatial learning (T-Maze) tests (i) immediately after the treatment and (ii) 30 days after the treatment, along with age matched normal and saline control rats. Results showed no change in open field behaviour, but showed improved retention and spatial learning performance at both time points of behavioural tests, indicating the memory enhancing property of CTR which implicates a permanent change in the brain of CTR treated rats.

A rare complication of hardware failure in neurostimulation. Report of two cases.

The authors report on a rare complication of neurostimulation. Two patients presented with a skin rash after undergoing neurostimulator implantation, and the implants were found to have faulty electrical insulation. The rash was centered over the source of current leak and disappeared when the problem was corrected.

Effects of REM sleep deprivation on cholinergic receptor sensitivity and passive avoidance behavior in clomipramine model of depression.

This study investigated the effects of REM (rapid eye movement) sleep deprivation (RSD) on the activity of central cholinergic receptors and passive avoidance retention in rats treated neonatally with clomipramine. Male rat pups treated with clomipramine (15 mg/kg, s.c.) twice daily from postnatal day 5 to 21 were subjected to RSD procedure at three months of age, for 4 days consecutively. In the post-RSD phase, RSD-control rats showed a significantly enhanced cholinomimetic-induced hypothermia and an improved retention in passive avoidance task. However, these measures were not significantly different in RSD-experimental group as compared to rats treated neonatally with saline. These results suggest that RSD reverses the sensitivity of central cholinergic receptors in rats given clomipramine neonatally, and this mechanism may be involved in mediating the antidepressant effects of RSD treatment in clomipramine model of depression.

Neuronal mechanisms of increased accessibility of unpleasant memories in helpless rats - a summary of present findings and implication.

Several studies in humans have indicated an association between enhanced retrieval of unpleasant memory and depressive moods. No analogy has so far been demonstrated in laboratory animals, however. A series of z-tperiments, therefore, was initiated in this laboratory with an aim to develop an analogous model of memory bias and to define the neuronal substrate that may account for the differential memory bias, in rats. This paper summarizes current results of these experiments and discusses the likely neuronal mechanism of the enhanced retrieval of unpleasant memories. Also, the implications of these experimental data in understanding the psychobiologicai aspects of "emotive biasing", so characteristics of human conditions like depression and post-traumatic stress disorders are discussed.

Hyperactivity of hypothalamic pituitary axis in neonatal clomipramine model of depression.

This study examined the integrity of hypothalamic-pituitary-adrenal (HPA) axis in clomipramine model of depression. Male rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.). At three months of age, serum corticosterone level was estimated before and after dexamethasone (100 microg/kg, s.c.) administration and after subjected to REM sleep deprivation (RSD) for 4 days consecutively. Data indicated enhanced baseline corticosterone levels and nonsuppression to dexamethasone in clomipramine treated rats. The corticosterone levels however, reversed to the levels of control group in rats subjected to RSD. These findings thus indicated for the first time an HPA hyperactivity in rats treated with clomipramine during neonatal period and are in harmony with cholinergic hypersensitivity reported earlier in this model of depression.

Alpha-helical CRF blocks differential influence of corticotropin releasing factor (CRF) on appetitive and aversive memory retrieval in rats.

This study examined whether corticotropin releasing factor (CRF), given prior to test, would produce an improved retrieval of aversive memory in the same way as pre-exposure to inescapable footshocks and the CRF antagonist, alpha-helical CRF 9-41 (a-h CRF), blocks this effect in rats. For this purpose animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0mA footshock) events were given intracerebroventricularly (i.c.v.) 20 min before testing, a single dose of 0.05, 0.1, 0.2 or 0.4 microgram/rat of CRF, or 5 micrograms/rat of a-h CRF, or both at 10 min interval. In the retention test conducted with the same training apparatus 72-hr after conditioning, CRF (0.05, 0.1 and 0.2 microgram) treated rats showed a dose-dependent increase in latencies to enter the previously shocked goalarm, with the absence of such a difference in responding to the nonshocked goalarm. The highest dose of CRF (0.4 microgram), however, increased the latencies to enter both the goalboxes. Alpha-helical CRF, administered 10 min before, antagonized the memory-enhancing effect of CRF. Further, CRF (0.1, 0.2 and 0.4 microgram) significantly decreased the total number of center entries in the open field, consistent with the view that i.c.v. administered CRF produces "anxiogenic-like" effect. Alpha-helical CRF reversed this effect. The effect of CRF on memory retrieval was similar to that seen following inescapable footshock in rats. The results thus suggest the possible involvement of central CRF mechanisms in the differential enhancement of memory of helplessness condition.

Scopolamine blocks the effects of swim stress on memory retrieval in rats.

This study examined whether application of swim stress improved retrieval of a passive avoidance memory and if pretreatment with the anticholinergic agent, scopolamine, blocked this effect on memory retrieval. Animals initially given a passive avoidance training session were subjected to either a two or four swim stress sessions (15 min each) with or without prior treatment of scopolamine (0.05 or 0.1 mg/kg). The retrieval performance in passive avoidance test and motor activity was assessed 24 hr after the last swim stress session. In an independent control experiment, the passive avoidance training and test were conducted respectively, 24 and 72 hr after the last of four swim stress sessions with or without prior injection of scopolamine (0.1 mg/kg). The results showed an enhanced performance for the passive avoidance task in rats subjected to four swim stress sessions in both experiments and scopolamine given 30 min prior to each stress session diminished this performance of animals in the passive avoidance test. Two swim stress sessions with or without scopolamine treatment caused no significant effects on the retrieval performance. Also, no significant difference was observed among the groups in motor activity following any of the stress treatments in the open field test. These results, thus suggested for the first time, a relationship among swim stress, cholinergic activity and avoidance memory processes.

Effects of central administration of arginine-vasopressin on aversive memory retrieval.

This study examined whether arginine-vasopressin (A-VP), given before the test would produce an improved retrieval of aversive memory, in the same way as pre-exposure to inescapable footshocks, in rats. For this purpose animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were administered (intracerebroventricular) a single dose of 2.5, 5, 10 or 20 ng/rat of A-VP, 20-min before testing. In the retention test conducted with the same training apparatus 72 h after conditioning, the peptide treated rats showed a dose-dependent increase in latencies to enter the previously shocked goalarm, with the absence of such a difference in responding to the non-shocked goalarm. This differential response was not observed in saline treated rats. This effect of peptide on memory retrieval was similar to that seen following inescapable footshock in rats. These results suggest the possible involvement of central vasopressinergic mechanisms in the differential enhancement of memory of helplessness condition.

Effects of p-chlorophenylalanine-induced depletion of brain serotonin on retrieval of appetitive and aversive memories.

This study examined whether depletion of central serotonin produces an improved retrieval of aversive memories in the same way as pre-exposure to inescapable footshocks, in rats. Animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were given i.c.v. 24 hr later a single dose of p-chlorophenylalanine (p-CPA). (100, 200, 400 micrograms/rat) or drug vehicle. The retention performance and activity were assessed 48 hr after treatment with this depletor. While lower doses of p-CPA selectively reduced serotonin levels in striatum and anterior cortex, higher doses reduced both serotonin and norepinephrine levels in hippocampus in a dose-dependent fashion. The depletor however, failed to produce a differential improvement of aversive memory retrieval. On the contrary, p-CPA reduced the latency to enter both, previously shocked and appetitively reinforced, goalboxes. The enhanced traversing behaviour in T-maze, together with an increased central entry in the open field that observed in depleted groups, might suggest an anxiolytic activity of p-CPA.

Effects of Celastrus paniculatus on passive avoidance performance and biogenic amine turnover in albino rats.

The effects of an indigenous drug, Celastrus oil, extracted from the seeds of Celastrus paniculatus on learning and memory in a two compartment passive avoidance task was studied in albino rats. The effects on the contents of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in the brain and on the levels of their metabolites both in the brain and urine were also assessed. Significant improvement was observed in the retention ability of the drug treated rats compared with the saline administered controls. The contents of NE, DA and 5-HT and their metabolites in the brain were significantly decreased in the drug treated group. The urinary metabolite levels were also significantly decreased except for total 3-methoxy-4-hydroxyphenyl glycol. These data indicate that Celastrus oil causes an overall decrease in the turnover of all the three central monoamines and implicate the involvement of these aminergic systems in the learning and memory process.

A study of antitrypsin and macroglobulin levels in serum and saliva of patients with gingivitis.

Periodontal diseases are associated with chronic inflammation. The destruction of connective tissue matrix is responsible for the pathogenesis of chronic inflammatory states. The degradation of matrix is initiated extra and pericellularly by proteinases produced locally at the inflammatory site. The regulation of these proteinases are by inhibitors present in serum and extravascular tissues, and it is the proteinase/proteinase inhibitor balance that determines the progression of chronic inflammatory state. Few contradicting studies are available on changes in the levels of proteinase inhibitors in serum in periodontal disease. The occurrence of these inhibitors in saliva has not been studied in detail. The present study was aimed at measuring the Proteinase inhibitors in serum and saliva of patients with periodontal disease.

Effects of neonatal clomipramine on cholinergic receptor sensitivity and passive avoidance behavior in adult rats.

The effects of neonatal treatment with clomipramine on the sensitivity of cholinergic receptor and passive avoidance behavior were studied to examine the activity of the central cholinergic system. Rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.) and at 3 months of age the thermic responses to three different doses of oxotremorine were measured. One day following oxotremorine challenge study, the animals were subjected to passive avoidance training and retention was measured 24-hr later. Clomipramine treated animals showed an enhanced cholinomimetic-induced hypothermia and an increased latency in passive avoidance test. These findings may reflect an altered sensitivity of central cholinergic system in rats given clomipramine as neonates. The results were compared to other animal models of depression.

Effects of ACTH and ACTH 4-10 on aversive memory retrieval in rats.

The aim of the study was to examine whether ACTH and ACTH-fragment 4-10, given before the test would produce a selectively enhanced retrieval of aversive memories, in the same way as preexposure to inescapable footshocks, in rats. For this purpose animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were administered (s.c.) a single dose of 10, 20 or 40 ug/rat of ACTH or 5, 10 or 20 ug/rat of ACTH-fragment 4-10, 20-min before testing. The retention test conducted in the same training apparatus 72-hrs after conditioning showed a dose-dependent increase in latencies to enter the previously shocked goalarm with the absence of such a difference in responding to the nonshocked goalarm, in ACTH and ACTH 4-10 treated groups. This differential response was not observed in saline treated rats. This effect of peptides on memory retrieval was similar to that seen following inescapable footshock in rats. The results suggest the possible involvement of ACTH in the differential enhancement of memory of helplessness condition.

Effects of DSP-4-induced depletion of brain norepinephrine on appetitive and aversive memory retrieval.

This study examined whether depletion of central norepinephrine produces an improved retrieval of aversive memories in the same way as pre-exposure to inescapable footshocks, in rats. Animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA footshock) events were given a single dose of DSP-4 (100, 200 or 400 micrograms/rat) or drug vehicle ICV 24 hr later. The retention performance and activity were assessed 48 hr after the treatment with this neurotoxin. DSP-4 had no effect on open field activities but enhanced latencies to enter both, previously shocked and appetitively reinforced, goalboxes. The data thus, suggest that central administration of DSP-4 does not result in selective enhanced aversive memories. On the contrary, post-trial NE depletion with this neurotoxin might interfere with the retrieval of previously learned association with appetitive stimuli. DSP-4 significantly reduced monoamines, depending upon the brain regions assayed and the doses studied. However, only decreased NE in striatum coincided with the memory changes suggesting that NE innervation to striatum may participate in the retrieval process.

Phenytoin and phenobarbital: a comparison of their state-dependent effects.

Two commonly used antiepileptic drugs, phenytoin sodium and phenobarbital sodium, were investigated for state-dependency effects at different doses. Male Wistar strain rats trained to a criterion in an inhibitory avoidance task and a food-motivated T-maze task under varying drug and nondrug states were subjected to retention tests 24 and 48 h, respectively, following acquisition. The treatment instituted at the time of retrieval was either the same as, or different from, that used during training. The results indicated that phenytoin produced state-dependency effects at test doses of 20, 40, and 60 mg/kg in the avoidance task and at test dose of 20 mg/kg in the T-maze task experiments. These state-specific effects were comparable to those of phenobarbital sodium (5 and 10 mg/kg). The reinstitution of the drug state in an additional test session produced approximately equal and significant recovery of conditioned responses in the T-maze paradigm both in phenytoin and phenobarbital groups. These results demonstrate, for the first time, the ability of phenytoin to produce state-dependency effects in a pattern similar to that observed with a widely studied compound such as phenobarbital. Overall, the data provide no support for the view that the degree of discriminability of a drug is an indicator of potential state-dependency effects and is restricted only to the dosage high enough to produce noticeable intoxication.

Effects of Nardostachys jatamansi on biogenic amines and inhibitory amino acids in the rat brain.

The effect of acute and subchronic administration of an alcoholic extract of the roots of Nardostachys jatamansi on norepinephrine (NE), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), gamma-aminobutyric acid (GABA), and taurine were studied in male albino Wistar rats. The acute oral administration of the extract did not change the level of NE and DA but resulted in a significant increase in the level of 5-HT and 5-HIAA. A significant increase in the level of GABA and taurine was observed in the drug-treated groups when compared to the controls. A 15-day treatment resulted in a significant increase in the levels of NE, DA, 5-HT, 5-HIAA, and GABA. These data indicate that the alcoholic extract of the roots of N. jatamansi causes an overall increase in the levels of central monoamines and inhibitory amino acids.