Browsing by Author "A.P. Sen"

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Advances in Contemporary Research. Prostaglandins modulate central serotonergic neurotransmission
(1989) S.K. Bhattacharya; G. Dasgupta; A.P. Sen
[No abstract available]
Anxiolytic activity of piracetam, a nootropic agent, following subchronic administration in rodents
(1993) S.K. Bhattacharya; A.P. Sen; S.N. Upadhyay; A.K. Jaiswal
Piracetam (PIR), a cyclic GABA derivative without GABA-mimetic activity, is classified as a nootropic agent, a new class of psychotropic drugs which augment learning acquisition and retention of memory. The present study indicates that PIR has significant anxiolytic activity in rodents following subchronic, but not acute administration, when tested against several paradigms of experimental anxiety. Thus, PIR (250 and 500 mg/kg), administered orally for 7 and 14 days, exhibited anxiolytic activity in the open-field, elevated plus-maze and footshock-induced fighting in paired mice paradigms, as well as in the Vogel's conflict test in rats. In addition, PIR induced significant reduction in rat brain tribulin levels, a putative endocoid marker for anxiety, produced by pentylenetetrazole, an anxiogenic agent. On the contrary, single acute administration of PIR failed to induce any anxiolytic effect. The present study, thus, confirms clinical reports that PIR can induce a delayed antianxiety effect in psychogeriatric individuals and in chronic alcoholism.
Central muscarinic receptor subtypes and carrageenin-induced paw oedema in rats
(Springer-Verlag, 1991) S.K. Bhattacharya; A.P. Sen; G. Das Gupta; K. Seth; P.K. Seth
In an earlier report from this laboratory, it was demonstrated that the central cholinergic system exerted a modulatory pro-inflammatory effect on carrageenin-induced paw inflammation in rats. In this study, the role of the central muscarinic receptors in cholinergic modulation of peripheral inflammation was investigated by using several M1 and M2 receptor agonists and antagonists. The M1 receptor agonists aceclidine and arecholine and the nonspecific muscarinic receptor agonist oxotremorine augmented carrageenin oedema, an effect attenuated by the M1 receptor antagonist scopolamine. Physostigmine behaved like a M1 receptor agonist at all dose levels. However, the other M2 receptor agonist, carbachol, produced a dose-dependent dual effect, with lower doses attenuating the oedema and higher doses augmenting the inflammation. While the former action appeared to be due to M2 receptor stimulation, because it was blocked by AF-DX 116-a M2 receptor antagonist, the latter action appeared to be induced by M1 receptor stimulation, because it was inhibited by scopolamine. The pro-inflammatory effect of the M2 receptor antagonists AF-DX 116 and gallamine appeared to be induced by enhanced neuronal release of acetyl-choline, because the effects were not evident following pretreatment with hemicholinium, which attenuates synthesis of the amine. Muscarinic receptor binding studies with (3H)-QNB indicated that the corpus striatum has substantially higher population of M1 receptors compared with the cerebellum. In the corpus striatum, (3H)-QNB binding indicated initial up-regulation followed by down-regulation of M1 receptors during peak inflammation, which appeared to persist even after a decrease in the inflammation. In contrast, the M1 receptors in the cerebellum appeared to be down-regulated very transiently during the early phase of the inflammation. While these receptor alterations may be due to the inflammation, it is equally possible that they represent changes induced by the stress of pain and inflammation induced by carrageenin. © 1991 Springer-Verlag.
Dopaminergic modulation of footshock induced aggression in paired rats
(1992) K.P. Datla; A.P. Sen; S.K. Bhattacharya
Footshock induced aggression (FIA) was induced in weight matched paired rats and three paradigms of aggressive behaviour was recorded, namely, the latency to fight (LF), total period of physical contact (TPP) and cumulative aggression scores (CAS). Dopamine (DA), administered centrally, and peripherally administered L-dopa (with benserazide, a peripheral decarboxylase inhibitor), a DA precursor, and the postsynaptic D2 receptor agonists, apomorphine, N-n-propyl-norapomorphine (PNA), bromocryptine, lisuride and pergolide, induced a dose-related facilitation of FIA characterized by decrease in LF and increase in TPP and CAS. However, the DA presynaptic receptor agonist, BHT-920, induced a biphasic effect with inhibition of FIA being induced by a lower dose and facilitation of the aggressive behaviour produced by a higher dose. The postsynaptic D2 receptor antagonists, haloperidol, spiperone and pimozide, induced a dose-related attenuation of FIA, and effect not seen with domperidone, a peripheral DA receptor antagonist. The results indicate that central dopaminergic postsynaptic D2 receptors have a modulatory facilitative effect on FIA, while the presynaptic DA autoreceptors mitigate aggressive behaviour. However, the presynaptic DA receptor agonist, BHT-920, appears to lose its receptor specificity on dose increment. Long term administration of haloperidol, followed by withdrawal, or desipramine, induced per se augmentation of FIA and potentiated the aggression-facilitative effects of L-dopa, apomorphine and PNA. Since both these treatments are known to induce supersensitivity of central postsynaptic dopamine D2 receptors, the effects are likely to be related to augmented function of dopamine neurones. The findings in conjunction with a recent report from this laboratory indicating an increase in rat brain DA levels in FIA, support the contention that the central DA system has a facilitative effect on FIA.
Effect of centrally administered enkephalins on carrageenin-induced paw oedema in rats
(Springer-Verlag, 1992) S.K. Bhattacharya; M. Saraswati; A.P. Sen
Intracerebroventricularly (icv) administered met-enkephalin, leuenkephalin, and morphine induced dose-related attenuation of carrageenin-induced acute paw oedema in rats. Naloxone (10 μ, icv) antagonized the anti-inflammatory effects of the enkephalins (20 μg) and morphine (20 μg), but itself induced an anti-inflammatory effect at a higher dose (50 μg, icv). The anti-inflammatory effects of the enkephalins, morphine, and the high dose of naloxone were significantly inhibited by metyrapone, an inhibitor of endogenous corticoid synthesis. The icv-administered doses of the enkephalins and morphine induced insignificant inflammation-attenuating effects when administered i.p. Results suggest that the anti-inflammatory effects of the enkephalins and morphine are exerted through central opiate receptors. Furthermore, the inflammation-attenuating effects of these drugs and the higher dose of naloxone appear to be dependent upon endogenous corticoids, suggesting that activation of the hypothalamo-pituitary-adrenocortical axis may be involved. © 1992 Springer-Verlag.
Effect of selective muscarinic receptor agonists and antagonists on active-avoidance learning acquisition in rats
(1991) A.P. Sen; S.K. Bhattacharya
[No abstract available]
Effects of muscarinic receptor agonists and antagonists on dopamine-mediated behavioural paradigms
(Springer-Verlag, 1991) S.K. Bhattacharya; A.P. Sen
The effects of some muscarinic M1 and M2 receptor agonists and antagonists on two dopamine-mediated behavioural paradigms, namely postswim grooming response and apormorphine-induced climbing behaviour, was investigated in mice. The M1 agonists and M2 receptor antagonists attenuated both paradigms, whereas the M1 receptor antagonists and M2 receptor agonists facilitated both behaviours. However, carbachol and physostigmine, exhibited a similar dose-dependent dual effect with the lower doses augmenting and the higher doses inhibiting both the behaviours, suggesting that the M2 agonist receptor specificity is lost on dose increment. The findings indicate that the central cholinergic muscarinic heteroreceptors, like the other muscarinic receptors, are functionally divisible into M1 and M2 receptor subtypes in their modulation of dopaminergic activity. © 1991 Springer-Verlag.
Effects of muscarinic receptor agonists and antagonists on rat brain serotonergic activity
(Springer-Verlag, 1992) S.K. Bhattacharya; A.P. Sen
The effects of some muscarinic M1 and M2 receptor agonists and antagonists on rat brain serotonergic activity was assessed by noting their effects on the levels of 5-hydroxytryptamine (5-HT) and its major metabolite, 5-hydroxyindole acetic acid (5-HIAA), estimated by a high pressure-liquid Chromatographie (HPLC) technique. The muscarinic M1 receptor agonists, arecholine and McN-A-343, and the M2 receptor agonists, gallamine and AF-DX 116, induced a dose-related decrease in the concentrations of both 5-HT and 5-HIAA. On the contrary, scopolamine and the selective M1 receptor antagonist, pirenzepine, increased the levels of the amine and its metabolite. The anticholinesterase agent, physostigmine, and the putative M2 receptor agonist, carbachol, induced a dose-related dual effect, with the smaller doses decreasing and the higher doses increasing 5-HT and 5-HIAA concentrations. The results indicate that an inverse relationship exists between the cholinergic and serotonergic neurotransmitter systems in the rat brain due to the likely presence of muscarinic heteroreceptors on serotonergic neurones. The data also indicates that though physostigmine and carbachol may function as M2 receptor agonists, they lose their receptor specificity on dose increment. © 1992 Springer-Verlag.
Effects of muscarinic receptor agonists and antagonists on response of non-extensor rats to maximal electroshock
(1991) S.K. Bhattacharya; A.P. Sen; S.K. Mitra
[No abstract available]
Effects of some selective muscarinic M1 and M2 receptor agonists and antagonists on rat brain dopaminergic activity
(1992) S.K. Bhattacharya; A.P. Sen
In this study, the effects of some selective muscarinic M1 and M2 receptor agonists on rat brain levels of dopamine (DA), and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was investigated using a high pressure liquid chromatographic (HPLC) technique. The rat brain DA, DOPAC and HVA levels in uncannulated and ip saline-administered control animals was not significantly different from their intracerebroventricular (i.c.v.) cannulated artificial cerebrospinal fluid-administered counterparts. The muscarinic M1 receptor agonists, arecholine (i.p.) and McN-343 (i.c.v.) increased DA concentrations while decreasing that of DOPAC and HVA. A similar feature was noted with the M2 receptor antagonists gallamine (i.c.v.) and AF-DX 116 (i.p.). On the contrary, the M1 receptor antagonists pirenzepine (i.c.v.) and scopolamine (i.p.) induced a decrease in DA levels with increase in DOPAC and HVA concentrations. The M2 receptor agonist, carbachol (i.c.v.), and physostigmine (i.p.) produced dose-dependent changes, with lower doses inducing an increase in levels of DA, DOPAC and HVA and higher doses tending to increase the amine concentrations while reducing brain levels of its metabolites. The results indicate that the muscarinic M1 and M2 receptors modulate rat brain DA activity by functioning as heteroreceptors on dopaminergic neurones. The M1 receptors appear to decrease dopaminergic activity whereas the M2 receptors function to augment DA release. However, the specificity of the M2 receptor agonist, carbachol, and physostigmine, appear to be lost on dose increment. The biochemical data garnered from this study corroborates the pharmacological data, from an earlier study from this laboratory, which indicated that M1 receptor agonists and M2 receptor antagonists attenuate DA-mediated behavioural paradigms, which are augmented by M1 receptor antagonists and M2 receptor agonists.
Latency of memory consolidation induced in mice by piracetam, a nootropic agent
(1993) S.K. Bhattacharya; S.N. Upadhyay; A.K. Jaiswal; A.P. Sen
Piracetam (PIR), a cyclic GABA derivative, is the prototype of a new class of psychoactive drugs, the nootropic agents, which improve learning acquisition and the retention of the learning as memory. It was proposed that nootropics act on processes essentially involved in information storage, thus facilitating memory. This property can best be investigated by drug administration after the learning trial and assessing subsequent retention performance. The present study was designed to evaluate the effective time period of memory consolidation, induced by piracetam, by assessing the retention of a learned task in two behavioural paradigms, following administration of the drug after learning acquisition. Physostigmine was used as the standard drug because of its well established facilitation of memory storage. PIR (250 and 500 mg/kg, ip) and physostigmine (0.05 mg/kg, ip) were administered in different groups of mice 5 min, 1, 2, 4, 8, 12 and 24 hr after learning acquisition of two passive avoidance tasks and the retention performance was evaluated 3 days later. The results indicate that, while physostigmine induced significant memory consolidation when administered up to 2 hr after learning acquisition, PIR induced retention of learning beyond this period. Thus, the highest effective post-trial interval for the lower and higher dose of the drug was 8 and 12 hr, respectively, in both the test paradigms. The results confirm that nootropics, like piracetam, are capable of memory consolidation, as assessed by retention of learning, even after intervals of 8 to 12 hr between learning and drug treatment.
Thermic response of selective muscarinic agonists and antagonists in rat
(1991) A.P. Sen; S.K. Bhattacharya
[No abstract available]