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Biomedical subjects

S K Kulkarni

Publications and source records attributed to S K Kulkarni.

At least 145 records · Page 8Linked to original sources
PubMed1993

Effect of D1- and D2-dopamine agonists on neocortical and hippocampal EEG activity of rat brain: modulation of rimcazole effect.

The effect of selective D1- and D2-dopamine (DA) receptor stimulation on neocortical and hippocampal electroencephalographic (EEG) activity of rat brain was studied. The modulation of the effect of rimcazole, a sigma receptor antagonist, by D1- and D2-DA receptor agonists was also investigated. B-HT 920 (0.5 mg/kg), a D2 DA agonist, produced significant inhibition of EEG activity in neocortex and hippocampus. The lower doses of B-HT 920 (0.1 and 0.25 mg/kg) either enhanced the frequency and amplitude of cortical and hippocampal firing or lacked any significant effect. The inhibitory effect of B-HT 920 was blocked by haloperidol (0.5 mg/kg), a D2-receptor antagonist and enhanced by idazoxan (1.0 mg/kg), an alpha 2-adrenoceptor antagonist. SKF 38393 (5.0 mg/kg), a D1-DA receptor agonist and dopamine (10 mcg/rat) or apomorphine (0.5 mg/kg), a mixed D1-/D2-agonist, also inhibited the frequency and amplitude of cortical and hippocampal EEG. A significantly higher inhibition of electrical activity was observed following concomitant administration of B-HT 920 (0.1 mg/kg) and SKF 38393 (5.0 mg/kg) in comparison with the effect of each drug alone. Rimcazole (6.0 mg/kg) increased the frequency of cortical and hippocampal firing. Amplitude of cortical firing was enhanced but not of hippocampal EEG following administration of rimcazole. Rimcazole blocked the effect of SKF 38393 (5.0 mg/kg) and apomorphine (0.5 mg/kg) but not of B-HT 920 (0.5 mg/kg) on cortical and hippocampal EEG, respectively. The above data suggests a modulatory effect of D1-receptor activation on the inhibitory effect of D2-receptor stimulation in cortex as well as hippocampus and the blockade by rimcazole of the effect of D1-DA receptor agonist in these areas.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Alprazolam modifies animal behaviour on elevated plus-maze.

Exposure to elevated plus-maze is known to evoke approach-avoidance conflict behaviour and anxiety related movements in mice. Alprazolam (0.1 to 1 mg/kg, ip) produced dose dependant increase in antianxiety response, 100% first preference to open arm, open arm entries and exploratory behaviour. This effect was not only comparable to diazepam but also sensitive to reversal by flumazenil, a benzodiazepine receptor antagonist. Withdrawal of alprazolam (2 mg/kg/day for 14 days) and diazepam (20 mg/kg/day for 14 days) from chronic treatment produced typical anxiety response in animals. When tested for transfer latency, a parameter for learning and memory, both diazepam and alprazolam interfered with cognitive behaviour. Besides these actions, alprazolam also possesses anti-depressant property which makes it an atypical benzodiazepine for anxiety, panic disorder and endogenous depression.

Alprazolam↗
PubMed1993

Protective effect of BR-16A (Mentat), a herbal preparation on alcohol abstinence-induced anxiety and convulsions.

Chronic administration of ethanol (2-5 g/kg, po) on days 1 to 6 and its withdrawal produced anxiogenic reaction in mice and rats as assessed on the elevated plus-maze. Daily administration of BR-16A (100 mg/kg) prior to ethanol intoxication for 6 days prevented withdrawal induced anxiety in both rats and mice. However, acute administration of a single dose of BR-16A, to animals withdrawn from ethanol, i.e. on the 7th day, showed significant anxiogenic response. Ethanol withdrawal also sensitized the convulsogenic reaction to pentylenetetrazole (PTZ). A non-convulsive dose (40 or 60 mg/kg) of PTZ produced full blown convulsions and increased mortality in ethanol withdrawn rats and mice, respectively. Both acute and chronic administration of BR-16A (100 mg/kg) exhibited significant protection against ethanol withdrawal-induced reduction in PTZ threshold in rats and mice. The results suggest the usefulness of this safe herbal psychotropic preparation in the management of ethanol withdrawal reactions.

Animals↗
PubMed1993

Evidence for benzodiazepine receptor interaction with MK 801 in anxiety related behaviour in rats.

Antianxiety effect of noncompetitive NMDA receptor antagonist MK 801 was investigated on elevated plus-maze paradigm in rats. Interactional effects of MK 801 with the specific anxiolytic agent, diazepam; the anxiogenic beta-carboline agent, FG-7142 and the central BZ receptor antagonist Ro 15-1788 were explored. MK 801 (0.025-0.1 mg/kg) produced anxiolytic effect at all the doses in rats. Effect was potentiated by diazepam in rats. Both, FG-7142 and Ro 15-1788 reversed the effects of MK 801 and diazepam, when these agents were concomitantly administered. The study revealed anxiolytic profile of MK 801 and indicates that NMDA receptors can modulate the benzodiazepine receptor activity in rodents in elevated plus-maze apparatus.

Animals↗
PubMed1993

(+/-)Baclofen sensitive scopolamine-induced short-term memory deficits in mice.

Possible involvement of GABA receptor systems in scopolamine-induced short-term memory deficits was investigated using latency of mice to reach shock-free zone (SFZ) and number of mistakes (descents) the animal made in 15 min as parameters for acquisition and retention of memory in passive avoidance paradigm. Atropine (1-5 mg/kg), scopolamine (0.1-0.5 mg/kg) but not pirenzepine (5-20 mg/kg) caused disruption of memory. GABA (50, 75 and 100 mg/kg) showed retention enhancing effects in scopolamine-treated and untreated animals but GABA agonist progabide (5-20 mg/kg) did not affect any of the parameter significantly. GABAA agonist, muscimol (0.05 and 0.1 mg/kg) and GABAB agonist, (+/-)baclofen (0.25, 0.5 and 1 mg/kg) and (-)baclofen (0.25 and 0.5 mg/kg) also displayed memory enhancing action. Whereas, GABAA antagonist, bicuculline produced hind limb rigidity, GABAB antagonist, CGP 35348 did not show any effect per se, but reversed the (+/-)baclofen-induced delay in latency, without affecting retention enhancing action of (+/-)baclofen. Combined administration of subeffective dose of GABA (50 mg/kg) and (+/-)baclofen (0.25 mg/kg), showed a significant improvement in acquisition and retention. However, the effect of GABA (100 mg/kg) on acquisition was reversed by bicuculline (2 mg/kg) and by CGP 35348 (100 mg/kg) while improving retention. The present study extends support to the cholinergic concept in cognitive performance and provide an evidence for the influence of GABAergic (particularly GABAB) modulation in scopolamine-induced learning and memory deficits in mice.

Animals↗
PubMed1992

Modulation of MK-801 response by dopaminergic agents in mice.

Various doses of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, MK-801 (0.1-0.5 mg/kg) and ketamine (2.5-10 mg/kg), produced a dose-dependent increase in stereotypic behaviour in naive mice. MK-801 (0.1 mg/kg) and ketamine (2.5 mg/kg) potentiated the stereotypic response of apomorphine (0.1-0.5 mg/kg) in mice pretreated with reserpine (5 mg/kg, 24 h prior) and alpha-methyl-p-tyrosine (150 mg/kg, 1 h prior) but not in naive mice. SKF 38393, a D1 dopamine agonist, enhanced whereas B-HT 920, a D2 dopamine agonist, reduced the stereotypic response of MK-801 in naive mice. The response of MK-801 was blocked by pretreatment with haloperidol (0.5 mg/kg), molindone (2.5 mg/kg), clozapine (7.5 mg/kg) and SCH 23390 (0.1 mg/kg). The present data suggest involvement of endogenous DA transmission in the stimulant action of non-competitive NMDA antagonists in mice. Dopamine D1 and D2 receptor stimulation, respectively, exert opposing effects on the behavioral expression of MK-801 in mice.

Animals↗
PubMed1992

D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in experimental catalepsy in rats.

Mixed D1/D2 dopamine (DA) antagonists, perphenazine (5 mg/kg) and haloperidol (2 mg/kg) induced catalepsy in rats. SCH 23390 (1 mg/kg), a D1 DA antagonist, also produced catalepsy. Co-administration of perphenazine (0.5 mg/kg) and SCH 23390 (0.1 mg/kg), at low doses, produced a marked increase in cataleptic response. B-HT 920, a D2 agonist, reversed the cataleptogenic effects of perphenazine, haloperidol and SCH 23390. SKF 38893 (5 mg/kg) reduced the cataleptogenic effect of SCH 23390 but failed to reverse haloperidol- or perphenazine-induced catalepsy. SKF 38393 (10 mg/kg), however, protected the animals against perphenazine- induced catalepsy. Combined administration of B-HT 920 (0.1 mg/kg) and SKF 38393 (5 mg/kg) enhanced the protective effect of B-HT 920 in SCH 23390-treated animals but not in animals treated with haloperidol or perphenazine. MK-801 (0.025-0.5 mg/kg), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, reduced the cataleptogenic effects of perphenazine, haloperidol as well as SCH 23390. The anticataleptic action of MK-801 was enhanced by scopolamine (0.1 mg/kg) but not by bromocriptine (1 mg/kg) or clonidine (0.05 mg/kg) in perphenazine-treated rats. Unlike B-HT 920 (0.1 mg/kg), SKF 38393 (5 mg/kg) potentiated the anticataleptic effect of MK-801 (0.01 mg/kg) against SCH 23390-induced catalepsy. The above data suggests D1/D2 interdependence in catalepsy and a modulatory role of D1 and D2 DA receptor stimulation on the anticataleptic effect of MK-801.

Animals↗
PubMed1992

Evaluation of learning and memory mechanisms employing elevated plus-maze in rats and mice.

1. The effect of drugs affecting learning and memory was investigated using transfer latency (TL) as parameter for acquisition and retention of memory process on elevated plus-maze both in rats and mice. Further the validity of the procedure was envisaged. 2. The results provide an evidence for utility of shortened TL on 2nd day trial in old rats and mice as a parameter for retention or consolidation of memory, while treatment of drugs 30 min prior to 1st day may also be utilised for acquisition related action of drugs. 3. The drugs producing acquisition deficits namely scopolamine (0.1-0.5 mg/kg) and MK 801 (0.05-0.1 mg/kg) did not affect the shortened TL on elevated plus-maze in rats while nootropics, like piracetam (150 mg/kg) and captopril (30 mg/kg) reduced the shortened TL. The memory enhancing effect of these agent was reversed by scopolamine (0.3 mg/kg) and MK 801 (0.1 mg/kg) both in rats and mice. The results suggested the acquisition affecting drugs, however, did not show any effect on retention parameter (shortened TL) but can reverse the retention facilitatory action of nootropics. The results also provide indirect evidence for participation of cholinergic and NMDA-receptor blockade in the mechanism of these drugs. 4. Scopolamine and MK 801 produced acquisition deficits in mice, as they increased the TL on 1st and 2nd day trial while physostigmine (0.05 mg/kg) decreased the 2nd day TL. Physostigmine (0.1 mg/kg) reversed scopolamine and MK 801 induced acquisition deficits suggested participation of cholinergic and NMDA- receptor in learning process. 5. The results validate the utility of the elevated plus-maze for evaluation of possible nootropic action of drugs.

Aging↗
PubMed1992

Prevention of development of tolerance and dependence to opiate in mice by BR-16A (Mentat), a herbal psychotropic preparation.

Chronic treatment with BR-16A (20-500 mg/kg) followed by saline on days 1 to 9 failed to produce any significant change in tail-flick latency from the saline-pretreated group in mice. Repeated administration of BR-16A(20-500 mg/kg) for 9 days however, attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg). BR-16A (20-500 mg/kg) also suppressed, in a dose-dependent manner, the development of morphine dependence as assessed by naloxone (2 mg/kg)-precipitated withdrawal on day 10 of testing.

Analysis of Variance↗
PubMed1992

Evidence for nootropic effect of BR-16A (Mentat), a herbal psychotropic preparation, in mice.

BR-16A (Mentat 50-500 mg/kg) improved acquisition and retention of a passive avoidance task in a step-down paradigm in mice. BR-16A (50-500 mg/kg) reversed scopolamine (0.3 mg/kg)-induced disruption of acquisition and retention. BR 16-A (50 and 100 mg/kg) attenuated amnesia produced by the acute treatment with electroconvulsive shock (ECS), immediately after training. Chronic treatment with ECS, for 6 successive days at 24 h interval, disrupted memory consolidation on the 7th day. Daily administration of BR-16A (50 and 100 mg/kg) for 6 days significantly improved memory consolidation in mice receiving chronic ECS treatment. BR-16A (20-500 mg/kg), administered on the 7th day, also attenuated the disruption of memory consolidation produced by chronic treatment with ECS. On elevated plus-maze, BR-16A (50 and 100 mg/kg) reversed scopolamine (0.3 mg/kg)-induced delay in transfer latency on the 1st day. The above data suggests a nootropic effect of BR-16A in naive and amnesic mice.

Animals↗
PubMed1991

Chronic electroconvulsive shock alters hypothermic response of B-HT 920 and SKF 38393 in rats.

The hypothermic response of B-HT 920, a D2-dopamine agonist remained unaltered while that of apomorphine, a mixed D1-/D2-agonist was significantly reduced following chronic electro-convulsive shock (ECS) treatment. SKF 38393 (5 mg kg-1), a selective D1-agonist potentiated the hypothermic response of B-HT 920 in non-ECS-treated rats. The response of the combination was, however, attenuated following chronic ECS treatment. These observations suggested a reduction in D1-receptor density following chronic ECS treatment in rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Dopamine receptor mediated hypothermic action of B-HT 920 in rats.

The hypothermic action of the thiazoloazepine derivative B-HT 920, an alpha 2-adrenoceptor agonist has been investigated in rats. B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)-azepine dihydrochloride) (0.25-1.0 mg kg-1 i.p.) induced a dose-dependent hypothermia. This peak effect was seen within 60-90 min and lasted up to 120 min. Its action was potentiated by the selective D1-dopamine agonist SKF 38393 and inhibited by the D2-antagonists haloperidol (1 mg kg-1) and sulpiride (100 mg kg-1). The hypothermic action of B-HT 920 was centrally mediated; i.c.v. administration of 10 micrograms produced a significant fall in rectal temperature which was sensitive to blockade by haloperidol. B-HT 920 also potentiated the hypothermic action of apomorphine (0.1 and 0.5 mg kg-1) in a haloperidol sensitive manner. Reserpine (5 mg kg-1 i.p.) pretreatment reduced the hypothermic response of B-HT 920 (0.5 mg kg-1) but sensitized the response due to the combination of B-HT 920 (0.5 mg kg-1) and apomorphine (0.1 mg kg-1). Neither the selective alpha 2-adrenoceptor antagonists, yohimbine (1 mg kg-1) or idazoxan (1 mg kg-1), the histamine antagonist mepyramine (10 mg kg-1) nor the 5-HT antagonist cyproheptadine (5 mg kg-1) inhibited B-HT 920-induced hypothermia. Similarly, the selective alpha 1-antagonist prazosin (1 mg kg-1) and the beta-antagonist propranolol (10 mg kg-1) failed to modify the hypothermic action of B-HT 920. These observations demonstrated hypothermia induced by B-HT 920 is mediated by postsynaptic D2-receptors and D1- and D2-receptor interplay is essential for the full expression of hypothermia in rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Alpha 2-adrenoceptor- and D2-dopamine receptor-mediated analgesic response of B-HT 920.

The involvement of D2-dopamine receptors in the antinociceptive action of B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-(4H) thiazolo-(4,5d)-azepine) has been investigated in mice. B-HT 920 (0.1-2.0 mg kg-1) and apomorphine (0.1-2.0 mg kg-1) produced a dose-dependent increase in tail flick latency. Analgesia induced by apomorphine was blocked by the D2-antagonist, haloperidol (1 mg kg-1) but not by the opioid antagonist, naloxone (1 mg kg-1). The antinociceptive action of B-HT 920 was potentiated by the D1-agonist SKF 38393 (5 mg kg-1), an action antagonized by haloperidol. The selective alpha 2-adrenoceptor blocking drug yohimbine (1 mg kg-1) and naloxone (1 mg kg-1) blocked the antinociceptive action of B-HT 920 (1 mg kg-1). Haloperidol, however, failed to modify the B-HT 920-induced increase in tail flick latency. B-HT 920 and apomorphine reversed reserpine (2 mg kg-1) 4 h-induced hyperalgesia. The reversing action of apomorphine was blocked by haloperidol but not by yohimbine. Thus, a role of alpha 2-adrenoceptors and D2-dopamine receptors is postulated in the antinociceptive action of B-HT 920.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Altered response to GABAergic agents following electro and chemo convulsions in mice.

Effects of GABAergic agents and that of electroconvulsive shock (ECS) treatment were studied on bicuculline and picrotoxin (PTX)-induced convulsions in mice. Neither acute nor chronic ECS had any significant effect on bicuculline-induced convulsions, whereas the latency for PTX-induced convulsions was delayed by both acute and chronic ECS. Baclofen treatment delayed significantly the latency for PTX-induced convulsions in animals which were subjected to both acute and chronic ECS, whereas in bicuculline-induced convulsions, it shortened the latency of convulsions 24 hr after acute ECS. Progabide delayed the bicuculline-induced convulsions except in the case of 24 hr after acute ECS and PTX-induced convulsions except in the case of animals treated chronically with ECS. Fengabine showed no significant effect on bicuculline-induced convulsions. However, on PTX-induced convulsions, the latency was delayed in animals not subjected to ECS and in those subjected to chronic ECS. The possible explanations for the alterations in the effect of GABAergic agents following electro and chemo convulsions are (i) differences in the nature of antagonism by bicuculline and PTX, (ii) alterations in receptor sensitivity or number, and (iii) alterations in the levels of endogenous neurotransmitters, the latter two resulting as a result of acute or chronic ECS.

Animals↗
PubMed1991

Baclofen analgesia in mice: a GABAB-mediated response.

The effect of baclofen, a GABAB agonist, has been studied in three antinociceptive tests (tail flick latency, hot plate method and acetic acid-induced writhing) in mice. In all three models, baclofen was found to elicit a dose-dependent antinociceptive effect. The observed antinociceptive effect was stereospecific, as the levo isomer of baclofen was found to be more potent than the racemic mixture. Baclofen also potentiated morphine analgesia. The antinociceptive effect of baclofen was reversed by both CGP 35348, a GABAB antagonist, and naloxone, an opioid antagonist, but not by bicuculline or picrotoxin, GABAA antagonists. However, in acetic acid-induced writhing, naloxone failed to reverse baclofen analgesia. The data suggest that the antinociceptive effect of baclofen is GABAB receptor-mediated and that there may be a GABAergic and opiate/or non-opiate interaction in eliciting the analgesic effect.

Analgesia↗
PubMed1991

GABA/BZ-and NMDA-receptor interaction in digoxin-induced convulsions in rats.

Digoxin (7.5 micrograms icv) induced 'pop-corn' type of convulsions and 100% mortality. The GABA-ergic agents produced varying degree of protection against digoxin-induced neurotoxicity. Diazepam (4 mg/kg) offered significant protection whereas pentobarbital (5 mg/kg) and baclofen (5 mg/kg) markedly reduced per cent mortality, but ethanol (2 g/kg), progabide (50 mg/kg) and muscimol (0.5 mg/kg) as well as GABA (50 mg/kg) could not offer significant protection in doses used. GABA-ergic agonists; GABA, baclofen, diazepam and pentobarbital when administered along with MK-801 (0.5 mg/kg) a non-competitive NMDA antagonist, a potentiation of anticonvulsant action of MK-801 was observed. MK-801 showed potent anticonvulsant profile in dose range (0.25-1 mg/kg) studied. A synergistic influence of Mg2+ and K+ ions on NMDA receptor antagonism was also observed. A role of GABA-ergic facilitation and NMDA antagonism as a potential anticonvulsant approach in digoxin-induced convulsions in rats has been suggested.

Animals↗