Evidence that 5‐hydroxytryptamine release in rat dorsal raphé nucleus is controlled by 5‐HT1A, 5‐HT1B and 5‐HT1D autoreceptors

Davidson, Charles S.; Stamford, Jonathan A.

doi:10.1111/j.1476-5381.1995.tb13321.x

Cited by 158 publications

(92 citation statements)

References 8 publications

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“…The 5-HT 1D receptor inhibits synaptic transmission (Jones et al, 1995) and acts as an autoreceptor in the mammalian raphe nucleus (Davidson and Stamford, 1995). The actions of 5-HT 1D receptor on Ca 2ϩ currents and its role in the sensory transmission have not been reported; therefore, our results are the first to show that 5-HT 1D receptors also are involved in limiting sensory transmission by inhibiting T-type and HVA Ca 2ϩ channels.…”

Section: Identity Of Serotonergic Receptorsmentioning

confidence: 61%

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Sun

Dale

1997

J. Neurosci.

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The primary sensory Rohon-Beard (R-B) neurons of Xenopus larvae are highly analogous to the C fibers of the mammalian pain pathway. We explored the actions of 5-HT by studying the modulation of Ca 2ϩ currents. In ϳ80% of the acutely isolated R-B neurons, 5-HT inhibited the high voltage-activated (HVA) currents by 16% (n ϭ 29) and the T-type currents by 24% (n ϭ 41). The modulation of the T-type and the HVA currents was mimicked by selective 5-HT 1A and 5-HT 1D agonists: 8-OH-DPAT and L-694,247. The effects of the agonists were blocked by their respective 5-HT 1A or 5-HT 1D antagonists: p-MPPI and GR127935, suggesting that both 5-HT 1A and 5-HT 1D receptors were involved. Approximately 70% of the actions of 5-HT on HVA currents was occluded by -conotoxin-GVIA (N-type channel blocker), whereas the rest of the modulation (ϳ30%) was occluded by Ͻ100 nM -agatoxin-TK (P/Q-type channel blocker). This suggests that 5-HT acts on N-and P/Q-type Ca 2ϩ channels. Neither the modulation of the T-type nor that of the HVA currents was accompanied by changes in their voltage-dependent kinetics. Cell-attached patch-clamp recordings suggest that the modulation of the T-type channel occurs through a membrane-delimited second messenger. We have studied the functional consequences of the modulation of T-type Ca 2ϩ channels and have found that these channels play a role in spike initiation in R-B neurons. Modulation of T-type channels by 5-HT therefore could modulate the sensitivity of this sensory pathway by increasing the thresholds of R-B neurons. This is a new and potentially important locus for modulation of sensory pathways in vertebrates.

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Section: Identity Of Serotonergic Receptorsmentioning

confidence: 61%

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Sun

Dale

1997

J. Neurosci.

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“…The 5-HT 1B receptor is found primarily at sites of serotonin release (i.e., synaptic terminals or axonal varicosities), and activation of these receptors inhibits serotonin release (Gothert 1992;Boschert et al 1994;Davidson and Stamford 1995). On non-serotonergic neurons, the 5-HT 1B receptor also is found near points of transmitter release and appears to inhibit the release of other transmitters such as acetylcoline, glutamate, and GABA (Gothert 1992).…”

Section: Discussionmentioning

confidence: 99%

Aggression Escalated by Social Instigation or by Discontinuation of Reinforcement (“Frustration”) in Mice Inhibition by Anpirtoline: A 5-HT1B Receptor Agonist

Almeida

2002

Neuropsychopharmacology

140

104

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Experiments with social instigation or the omission of scheduled reinforcement show that serotonergic mechanisms may be involved in escalated aggression in animals. 5-HT 1B receptor agonists have anti-aggressive effects in individuals who show moderate as well as high levels of aggression. The present study compared the effects of the 5-HT 1B agonist anpirtoline (0.125-1.5 mg/kg) on (1) species-typical aggressive behavior in male mice, (2) aggression "instigated" or primed by prior exposure to the opponent, and (3) aggression heightened by "frustration" caused by omission of scheduled reinforcement. The effects of anpirtoline on species-typical behavior were also assessed after pretreatment with the 5-HT 1B/1D receptor antagonist GR127935 (10 mg/kg). Anpirtoline, like other 5-HT 1Bagonists 253, zolmitriptan) The development of valid experimental protocols that model clinically relevant, excessive levels of aggressive behavior is a continuing challenge for pre-clinical research on aggression (Miczek 2001). The leading neurobiological hypothesis attributes such intense aggressive behavior, often related to expressions of impulsivity, to a deficit in brain serotonin (Linnoila et al. 1983;Virkkunen et al. 1989;Coccaro 1989). An early example of this research strategy was the demonstration that mice would exhibit intense aggressive behavior after prolonged isolated housing, and this isolation-induced aggression is associated with lower serotonin turnover in the brainstem ). Long-standing concerns with the validity and reliability of isolation-induced aggression and its limited species generality prompt the search for alternate approaches (Brain 1975;Krsiak 1975). Similarly, correlation of aggressive behavior with a single tissue or CSF measurement of serotonin or its metabolite need to be reconciled with the anti-aggressive effects of agonist NO . 2 and antagonist treatment of specific serotonin receptor subtypes (Olivier et al. 1995;de Almeida et al. 2001).The exposure of an experimental subject to a potential rival for a short time prior to the actual confrontation engenders intense levels of aggression, as originally described in mice (Lagerspetz 1969;Tellegen and Horn 1972). For example, mice, rats, and hamsters initiate attacks with very short latency and at high frequency when tested with an intruder in their home cage or in an unfamiliar locale after having been provoked previously by an opponent (Potegal 1992;Fish et al. 1999). Instigation or priming is specific for increasing aggressive behavior and does not activate locomotion, feeding, or sexual behavior (Lagerspetz and Hautojarvi 1967;Potegal and Tenbrink 1984;Potegal 1992). Even after removal of the instigating or priming stimulus, high levels of aggression persist in fish and rodents, presumably from increased "aggressive arousal" or "attack readiness" (Heiligenberg 1974;Potegal and Tenbrink 1984;Potegal 1992). At the neurochemical level, animals that have been instigated to fight are characterized by a long-lasting decrease in serotonin in hypoth...

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“…Nevertheless, the agent is an effective 5-HTlD antagonist in rat central nervous system. Recently, GR 127935 (0.05 JM) has been shown to be an antagonist of sumatriptan in rat brain slices but not to block 5-HTIB autoreceptors (Davidson & Stamford, 1995). Given the crucial importance of GR 127935 as an identifying ligand, the identity of the ketanserin-sensitive receptor as a 5-HT1m receptor must remain unconfirmed.…”

Section: Discussionmentioning

confidence: 99%

Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

Manuel¹,

Wallis²,

Crick³

1995

British J Pharmacology

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1 The monosynaptic reflex (MSR), recorded in vitro from the neonatal rat spinal cord, was depressed by 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), methysergide and R( + )-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), and also by the selective 5-HTlD agonists, sumatriptan and N-methyl-3-(1-methyl-1-piperidinyl)-1H-indole-5-ethane sulphonamide (GR 85548).2 Ketanserin (1 gM) and methiothepin (1 gM) reduced the duration of depressions elicited by 5-CT, but not those produced by 5-HT, sumatriptan, GR 85548, methysergide or 8-OH-DPAT.3 The IC50 for MSR depression by 5-CT was 3.6, 2.1 -6.2nM (n=4), by sumatriptan was 15.2, 12.9-18.0nM (n=32), by GR 85548 was 18.4, 11.7-29.1 nM (n =12), by methysergide was 29.8, 10.2-87.1nM (n=4) and by 8-OH-DPAT was 0.21, 0.11-0.43 MM (n=3) (geometric means and 95% confidence limits). 4 Ketanserin (0.1 or 1 UM) antagonized competitively responses to sumatriptan (apparent pA2 7.8 ± 0.1, n = 5), GR 85548 (apparent pA2 7.6, unpaired data, n = 5), methysergide (apparent pA2 7.9 ± 0.12, n=4) and 8-OH-DPAT (apparent pA2 8.3 ± 0.1, n= 3). Concentration-response curves to 5-CT showed a smaller, parallel shift to the right (apparent pA2 6.8 ± 0.1, n = 4), but responses to 5-HT were unaffected by ketanserin (1 gM) (n = 4). Neither with these concentrations nor with concentrations in the range 1-3 nm was there any unequivocal blockade of responses to sumatriptan. 9 It is concluded that sumatriptan, GR 85548, methysergide and 8-OH-DPAT depress the MSR in the neonate rat spinal cord via ketanserin-sensitive receptors, which have some similarities to 5-HTLIT1 receptors but which are not blocked by GR 127935. 5-HT released by tryptaminergic pathways may act via the same receptors to depress the MSR. 5-HT applied to the cord probably acts via a different, possibly novel 5-HT receptor to depress the MSR.

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Evidence that 5‐hydroxytryptamine release in rat dorsal raphé nucleus is controlled by 5‐HT_1A, 5‐HT_1B and 5‐HT_1D autoreceptors

Cited by 158 publications

References 8 publications

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Aggression Escalated by Social Instigation or by Discontinuation of Reinforcement (“Frustration”) in Mice Inhibition by Anpirtoline: A 5-HT1B Receptor Agonist

Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

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Evidence that 5‐hydroxytryptamine release in rat dorsal raphé nucleus is controlled by 5‐HT1A, 5‐HT1B and 5‐HT1D autoreceptors

Cited by 158 publications

References 8 publications

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca2+Currents in the Primary Sensory Neurons ofXenopusLarvae

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca2+Currents in the Primary Sensory Neurons ofXenopusLarvae

Aggression Escalated by Social Instigation or by Discontinuation of Reinforcement (“Frustration”) in Mice Inhibition by Anpirtoline: A 5-HT1B Receptor Agonist

Ketanserin‐sensitive depressant actions of 5‐HT receptor agonists in the neonatal rat spinal cord

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Evidence that 5‐hydroxytryptamine release in rat dorsal raphé nucleus is controlled by 5‐HT_1A, 5‐HT_1B and 5‐HT_1D autoreceptors

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae