Imperial College London


Faculty of MedicineDepartment of Brain Sciences

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11 results found

File SE, Seth P, 2003, A review of 25 years of the social interaction test., Eur J Pharmacol, Vol: 463, Pages: 35-53, ISSN: 0014-2999

The social interaction test of anxiety was developed 25 years ago to provide an ethologically based test that was sensitive to both anxiolytic and anxiogenic effects. It is sensitive to a number of environmental and physiological factors that can affect anxiety. It has detected anxiogenic effects of peptides such as corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH), and anxiolytic effects of neuropeptide Y and substance P receptor antagonists. It has successfully identified neuropharmacological sites of action of anxiogenic compounds and drug withdrawal. Effects of compounds acting on the gamma-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) systems have been extensively investigated after both systemic administration and microinjection into specific brain regions. The use of this test has, thus, played a crucial role in unravelling the neural basis of anxiety. It is hoped that in the next 25 years, the test will play a crucial role in determining the genetic basis of anxiety disorders.

Journal article

Tucci S, Cheeta S, Genn RF, Seth P, File SEet al., 2002, Anxiety conditioned to nicotine in the elevated plus-maze is time dependent., Behav Pharmacol, Vol: 13, Pages: 615-620, ISSN: 0955-8810

Conditioning to the anxiogenic effects of nicotine has previously been demonstrated in the social interaction test and there was no generalization of conditioning between the social interaction and elevated plus-maze tests. Because the two tests generate distinct states of anxiety, the conditioning could have occurred to the cues associated with the test environment and/or to those associated with the type of anxiety generated by the test. The elevated plus-maze permits separation of these two factors, because quite distinct states of anxiety are generated on trials 1 and 2, whereas the apparatus cues remain the same. Rats that had been tested on day 1 in the plus-maze, 5 min after nicotine (0.45 mg/kg), showed a conditioned anxiogenic response when tested undrugged on day 2. This was shown by significantly lower percentages of open-arm entries and percentage of time spent on the open arms, compared with control groups. Thus, conditioning to apparatus cues is sufficient to mediate a conditioned anxiogenic effect. The importance of the timing of the nicotine-associated cues was demonstrated by the failure to obtain conditioned anxiogenic effects when rats were exposed to the plus-maze on day 1, 30 min after nicotine (0.45 or 0.1 mg/kg).

Journal article

Gupta S, Chaudhuri T, Seth P, Ganguly DK, Giri AKet al., 2002, Antimutagenic effects of black tea (World Blend) and its two active polyphenols theaflavins and thearubigins in Salmonella assays, Phytother Res, Vol: 16, Pages: 655-661

Journal article

Seth P, Cheeta S, Tucci S, File SEet al., 2002, Nicotinic--serotonergic interactions in brain and behaviour., Pharmacol Biochem Behav, Vol: 71, Pages: 795-805, ISSN: 0091-3057

This review focuses on nicotinic--serotonergic interactions in the central nervous system (CNS). Nicotine increases 5-hydroxytryptamine (5-HT) release in the cortex, striatum, hippocampus, dorsal raphé nucleus (DRN), hypothalamus, and spinal cord. As yet, there is little firm evidence for nicotinic receptors on serotonergic terminals and thus nicotine's effects on 5-HT may not necessarily be directly mediated, but there is strong evidence that the 5-HT tone plays a permissive role in nicotine's effects. The effects in the cortex, hippocampus, and DRN involve stimulation of 5-HT(1A) receptors, and in the striatum, 5-HT(3) receptors. The 5-HT(1A) receptors in the DRN play a role in mediating the anxiolytic effects of nicotine and the 5-HT(1A) receptors in the dorsal hippocampus and lateral septum mediate its anxiogenic effects. The increased startle and anxiety during nicotine withdrawal is mediated by 5-HT(1A) and 5-HT(3) receptors. The locomotor stimulant effect of acute nicotine is mediated by 5-HT(1A) receptors and 5-HT(2) receptors may play a role in the expression of a sensitised response after chronic nicotine treatment. Unfortunately, the role of 5-HT(1A) receptors in mediating nicotine seeking has not yet been investigated and would seem an important area for future research. There is also evidence for nicotinic--serotonergic interactions in the acquisition of the water maze, passive avoidance, and impulsivity in the five-choice serial reaction task.

Journal article

Seth P, Gajendiran M, Ganguly DK, 1997, Desensitization of spinal 5-HT1A receptors to 8-OH-DPAT: an in vivo spinal reflex study., Neuroreport, Vol: 8, Pages: 2489-2493, ISSN: 0959-4965

Serotonergic influence on spinal monosynaptic transmission and the desensitization of spinal 5-HT1A receptors following a single pretreatment with a 5-HT1A ligand were examined in vivo in acutely spinalized adult rats. Administration of a selective 5-HT1A agonist, 8-OH-DPAT (0.1 mg kg-1) significantly depressed the monosynaptic mass reflex (MMR) amplitude, which was prevented effectively by S(-)-propranolol, a 5-HT1A antagonist. The inhibitory effect of 8-OH-DPAT on MMR amplitude was significantly attenuated with a single dose of 8-OH-DPAT (1 mg kg-1, s.c.) administered 24 h before the experiments, indicating a marked desensitization of spinal 5-HT1A receptors. Desensitization of 5-HT1A receptors could be reversed by treatment of spiperone (1 mg kg-1, i.p.) 3 h before 8-OH-DPAT pretreatment. These results demonstrate that 5-HT1A receptor functionally modulates the spinal motor output and confirms the ability of 8-OH-DPAT to desensitize presynaptic 5-HT1A receptors as observed for the first time in rat spinal cord.

Journal article

Gajendiran M, Seth P, Ganguly DK, 1996, Involvement of the presynaptic dopamine D2 receptor in the depression of spinal reflex by apomorphine., Neuroreport, Vol: 7, Pages: 513-516, ISSN: 0959-4965

The relative roles of D1 and D2 dopamine (DA) receptors in mediating apomorphine (APO)-induced changes in the spinal reflex was investigated. Low doses of APO, a DA receptor agonist (0.2 mg kg-1, i.v.), depressed the monosynaptic mass reflex (MMR) in spinalized rats. Pretreatment with the D2-specific antagonist, spiperone, 10 min before APO prevented the APO-induced MMR depression. Pretreatment with the D1 antagonist SCH 23390 failed to prevent the APO-induced depression. Interestingly, SCH 23390 pretreatment preferentially antagonized the depression induced by a high dose of APO (3 mg kg-1, i.v.). Pretreatment with SKF 38393, a selective D1 agonist, completely prevented the APO-induced MMR depression. These results suggest that inhibition of spinal transmission by low dose of APO may be mediated through its action on presynaptic D2 receptors and that D1 and D2 receptors are functionally coupled at the spinal level in modulating the spinal motor output.

Journal article

Seth P, Gajendiran M, Maitra KK, Ross HG, Ganguly DKet al., 1993, Evidence for D1 dopamine receptor-mediated modulation of the synaptic transmission from motor axon collaterals to Renshaw cells in the rat spinal cord., Neurosci Lett, Vol: 158, Pages: 217-220, ISSN: 0304-3940

The possible modulatory role of D1 dopamine receptors on the excitability of lumbar spinal Renshaw cells was studied in anesthetized rats spinalized at T4 level. Burst responses elicited by single electrical shocks to ipsilateral ventral roots L6 (frequency 0.5 Hz, stimulus width 0.1 ms) and spontaneous activity were recorded extracellularly using conventional 3 M KCl filled glass micropipettes. The specific D1 agonist SKF 38393 (0.5-1 mg/kg i.v.) enhanced Renshaw cell burst responses by 20-60% (n = 7) and increased their spontaneous discharge rate (n = 3). This effect was clearly antagonized by the specific D1 antagonist SCH 23390 (1 mg/kg i.v.) although SCH 23390 proved ineffective per se. We conclude that SKF 38393 induced facilitation was due to activation of the specific D1 receptors which could be the functional counterpart of the presynaptic D2 receptors described earlier by us in the same synapse.

Journal article

Maitra KK, Seth P, Thewissen M, Ross HG, Ganguly DKet al., 1993, Dopaminergic influence on the excitability of antidromically activated Renshaw cells in the lumbar spinal cord of the rat., Acta Physiol Scand, Vol: 148, Pages: 101-107, ISSN: 0001-6772

The interaction between dopaminergic and cholinergic systems in the mammalian central nervous system, which is thought to have important implications in the pathophysiology of major extrapyramidal disorders, has never been adequately demonstrated in vivo. Renshaw cell burst responses to single electrical shocks to lumbar ventral roots in spinalized and decerebrated rats were studied. In this monosynaptic cholinergic pathway, apomorphine, a dopaminergic receptor agonist, inhibited whereas the D2-antagonist sulpiride facilitated the burst responses. The mutual antagonism of the two drugs and the depression coupled with the faster decay of post-tetanic potentiation of Renshaw cells by apomorphine demonstrate the involvement of presynaptic D2-receptors through which dopamine can modulate acetylcholine-mediated central synaptic transmission in vivo. The study also provides further evidence for the involvement of the spinal cord in extrapyramidal disorders.

Journal article

Maitra KK, Seth P, Ross HG, Thewissen M, Ganguly DKet al., 1992, Presynaptic dopaminergic inhibition of the spinal reflex in rats., Brain Res Bull, Vol: 28, Pages: 817-819, ISSN: 0361-9230

Dopaminergic influence on spinal monosynaptic transmission was examined in rats. Monosynaptic mass reflex (MMR) was recorded from the ventral root L6 following supramaximal stimulation (0.2 Hz; 0.1 ms) to the ipsilateral dorsal root L6 in spinalized rat under pentobarbitone sodium (40 mg/kg, i.p.) anaesthesia. MMR was inhibited by intravenous administration of the dopaminergic agonist, apomorphine (50-200 ug/kg) in a dose-dependent manner. The attenuatory effect of apomorphine (200 ug/kg i.v.) on the reflex could be reversed by the dopaminergic antagonist haloperidol (0.5 mg/kg, i.v.). Under tetanic stimulation (200 Hz; 15s), the pretetanic relative inhibition induced by apomorphine (200 ug/kg, i.v.) was increased only for a short period immediately after the cessation of tetanic stimulation. The results indicate existence of presynaptic dopamine receptors on the afferent terminals converging on the motoneurone which may functionally modulate the spinal motor output.

Journal article

Maitra KK, Seth P, Mohanakumar KP, Ganguly DKet al., 1992, Supersensitivity of spinal dopaminergic receptors in rat after chronic haloperidol., Brain Res Bull, Vol: 28, Pages: 133-135, ISSN: 0361-9230

In order to examine the effect of chronic neuroleptics on spinal dopaminergic system, rats were treated with haloperidol (0.5 mg/kg IP) for 21 days and the monosynaptic mass reflex (MMR) as well as dopamine (DA) metabolism were investigated. MMR, recorded from ventral root L6 following supramaximal stimulation to ipsilateral dorsal root L6 in spinalized rats, were found to be unaffected following chronic haloperidol treatment when compared to control. Apomorphine (0.1 mg/kg IV) caused 10-20% depression of MMR in control animals which was augmented to 40-50% in chronically haloperidol-treated animals suggesting an upregulation of DA receptors in the spinal cord. DA content of lumbar region of the spinal cord was unaffected whereas its major metabolite, homovanillic acid, was significantly reduced in chronic haloperidol-treated animals. This decreased utilization of DA may compensate the upregulation of DA receptors to maintain the physiological homeostasis of the spinal dopaminergic system.

Journal article

Seth P, Maitra KK, Ganguly DK, 1991, Haloperidol on rat phrenic hemidiaphragm., Arch Int Pharmacodyn Ther, Vol: 310, Pages: 87-93, ISSN: 0003-9780

The butyrophenone neuroleptic haloperidol (10.65-85.2 microM) blocked the indirectly elicited twitch response of rat phrenic nerve diaphragm preparation. The depression was poorly reversible and was not mediated through dopamine receptors since neither dopamine nor apomorphine could alter the haloperidol blockade. Experiments on the isolated phrenic nerve indicated that the excitability of the nerve was blocked by haloperidol (42.6 microM) and that this blocking effect was minimized in presence of a high concentration of Ca2+ (5 mM) in the bathing fluid. Haloperidol (10.65-85.2 microM) also concentration-dependently inhibited acetylcholine (2.7 microM) contracture, without affecting the potassium chloride (0.5 M) and caffeine (15 mM) contracture. We conclude that haloperidol acts as a local anaesthetic on the motor nerve, probably by affecting calcium channels.

Journal article

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