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Biomedical subjects

K B Kumar

Publications and source records attributed to K B Kumar.

At least 19 recordsLinked to original sources
PubMed2000

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.

Animals↗
PubMed1999

Studies on the euglycemic and hypolipidemic potentials of the novel indole analogue of thiazolidinedione, DRF 2189.

Euglycemic and hypolipidemic activities of a novel indole analogue of thiazolidinedione, DRF 2189 (CAS 172647-53-9), have been evaluated in different animal models. Compared to troglitazone (CAS 97322-87-7), DRF 2189 exhibited interesting plasma glucose and triglyceride lowering activity in genetically diabetic and obese db/db mice. It also produced a significant reduction in plasma glucose, triglyceride, total cholesterol levels and improvement in oral glucose tolerance in another genetic mouse model, the ob/ob mice. In high-fat diet fed Sprague-Dawley rats, DRF 2189 treatment showed improvement in plasma lipid parameters. Like other thiazolidinediones, this compound also possesses peroxisome proliferator activated receptor gamma (PPAR gamma) transactivation potential. In anaesthetized rat experiment, DRF 2189 produced a transient fall in blood pressure without any change in the ECG pattern. It showed non-specific smooth muscle relaxant activity against acetylcholine, histamine and potassium chloride induced contractions in isolated guinea pig ileum. A twenty-eight-day toxicity study in Wistar rats did not show any signs of treatment related adverse effects. The overall antidiabetic and hypolipidemic activities of DRF 2189 are comparable with rosiglitazone (CAS 155141-29-0) and superior to troglitazone. In conclusion, results from these preclinical studies indicate that DRF 2189, a novel thiazolidinedione, has a marked potential for the management of type-2 diabetes.

Animals↗
PubMed1998

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.

Animals↗
PubMed1997

Discriminated approach-avoidance task--a new paradigm for measuring both appetitive and aversive memory processes under identical test conditions.

Research on mnemonic processes in rats has predominantly made use of either appetitively or aversively motivated tasks. These behavioral paradigms are popular because rats are easily trained and a range of stimuli and response alternatives are available. Also, these paradigms have been generally found to be sensitive to pre- and post-trial manipulations with a variety of drugs having hypo- and hypermnesic effects. However, the available procedures do not permit a qualitative analysis of the memory changes, namely, a dissociation between the effect of a compound under study on the memory for pleasant versus unpleasant events, under the same experimental conditions. The discriminated approach-avoidance paradigm presented here is a novel method that enables this to be investigated quite easily, in rats. This behavioral paradigm was developed originally to assess the retrieval bias in the learned helplessness condition, and subsequently has been employed in studies of the pharmacological effects of several stress-related neuropeptides on appetitive and aversive memory processes.

Animals↗
PubMed1996

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.

Animals↗
PubMed1996

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.

Animals↗
PubMed1995

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.

Animals↗
PubMed1995

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.

Animals↗
PubMed1995

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.

Adrenocorticotropic Hormone↗
PubMed1995

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.

Animals↗
PubMed1994

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.

Animals↗
PubMed1994

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.

Animals↗
PubMed1993

Enhanced processing of an aversive memory following inescapable shock in rats.

The aim of the present study was to determine the effect of inescapable shock on appetitive and aversive memory retrieval. Rats conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0 mA) events were subjected, respectively, to inescapable, escapable, and no-shock stress treatments. A retention test conducted 48 hr following exposure to stress treatments showed an enhanced avoidance behavior to enter a previously shocked goalbox with the absence of such a difference in responding to the nonshocked goalbox by the animals exposed to inescapable footshock stress. This differential response was not observed in two other groups, one given escapable footshock and the other no shock at all. This finding suggests memory processing is selectively enhanced in the helplessness condition and parallel to the retrieval bias that is evidenced in humans in depressive mood and induced helplessness.

Animals↗
PubMed1993

Dyshormonogenetic goitre.

Thirty-seven patients with dyshormonogenetic goitre seen in the last five years are discussed. Males were as frequently affected as females. The peak incidence was in the second decade. The commonest presentation was a multinodular goitre with patent or subclinical hypothyroidism. Surgery was avoided except for gross disfigurement or presence of malignancy. Surgery done was near total thyroidectomy. All patients treated conservatively and those who were operated on have been advised life-long thyroxin therapy.

Adolescent↗
PubMed1992

Teratogenic effects of methyl parathion in developing chick embryos.

The effect of methyl parathion (MP) on developing chick embryos was investigated. The embryos were exposed at different stages of development to various doses of MP via the yolk sac route. This resulted in retarded growth which included reduced body weight and reduced body length and length of leg bones. Other teratogenic signs observed were short neck, muscular hypoplasia of legs, abdominal hernias and haemorrhagic spots in brain and upper body. These findings suggest that MP was a teratogen when injected into the yolk sacs of developing embryos.

Abnormalities, Drug-Induced↗
PubMed1991

Enhanced retrieval of unpleasant memory in helpless rats.

Several studies in humans have indicated an association between enhanced retrieval of unpleasant events and depressive mood. No analogy has so far been demonstrated in animals, however. The purpose of the present study was to determine the effect of learned helplessness on the retrieval of unpleasant memory in rats. Animals initially exposed to a single unpleasant event in a passive avoidance task were subjected, respectively, to inescapable, escapable, or no shock stress exposure. A retention test conducted 48 hr following stress exposure showed an enhanced performance for the passive avoidance task in rats subjected to inescapable shock stress. This improved performance was not observed in escapable or no shock stress groups. This finding in the learned helplessness condition in rats, is qualitatively similar to that found in humans in depressive mood.

Affect↗