Clark MS, Neumaier
The 5-HT1B receptor: behavioral implications.
Psychopharmacol Bull 2001 Autumn;35(4):170-85
"5-HT1B receptors are expressed
throughout the mammalian central nervous system. These receptors are located in
the axon terminals of both serotonergic and nonserotonergic neurons, where they
act as inhibitory autoreceptos or heteroreceptors, respectively. 5-HT1B receptors
inhibit the release of a range of neurotransmitters, including serotonin, GABA,
acetylcholine, and glutamate. These receptors have been difficult to study because
of the diversity of their cellular localization and the absence of highly selective
agonists and antagonists. There has been accumulating evidence, however, that
5-HT1B receptors modulate drug reinforcement, stress sensitivity, mood, anxiety,
and aggression. The general results of a number of studies suggest that reduced
5-HT1B heteroreceptor activity may increase impulsive behaviors, whereas reduced
5-HT1B autoreceptor activity may have an antidepressant-like effect. This review
focuses on the evidence from animal studies and human genetics that suggest that
5-HT1B receptors may be involved in the mechanism of action of antidepressants
and may become important targets of drug therapy in the future." [Abstract]
MD, Goadsby PJ, Roon KI, Lipton RB.
Triptans (serotonin, 5-HT1B/1D
agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials.
Cephalalgia 2002 Oct;22(8):633-58
"The triptans, selective serotonin
5-HT1B/1D agonists, are very effective acute migraine drugs. Soon, seven different
triptans will be clinically available at 13 different oral doses, making evidence-based
selection guidelines necessary. Triptan trials have similar designs, facilitating
meta-analysis. We wished to provide an evidence-based foundation for using triptans
in clinical practice, and to review the methodological issues surrounding triptan
trials. We asked pharmaceutical companies and the principal investigators of company-independent
trials for the 'raw patient data' of all double-blind, randomized, controlled,
clinical trials with oral triptans in migraine. All data were cross-checked with
published or presented data. We calculated summary estimates across studies for
important efficacy and tolerability parameters, and compared these with those
from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials,
53 (12 not yet published) involving 24089 patients met the criteria for inclusion.
Mean results (and 95% confidence intervals) for sumatriptan 100 mg, the first
available and most widely prescribed oral triptan, are 59% (57-60) for 2 h headache
response (improvement from moderate or severe to mild or no pain); 29% (27-30)
for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free
(pain free by 2 h and no headache recurrence or use of rescue medication 2-24
h post-dose), and 67% (63-70) for consistency (response in at least two out of
three treated attacks); placebo-subtracted proportions for patients with at least
one adverse event (AE) are 13% (8-18), for at least one central nervous system
AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these
data: rizatriptan 10 mg shows better efficacy and consistency, and similar tolerability;
eletriptan 80 mg shows better efficacy, similar consistency, but lower tolerability;
almotriptan 12.5 mg shows similar efficacy at 2 h but better sustained pain-free
response, consistency, and tolerability; sumatriptan 25 mg, naratriptan 2.5 mg
and eletriptan 20 mg show lower efficacy and better tolerability; zolmitriptan
2.5 mg and 5 mg, eletriptan 40 mg, and rizatriptan 5 mg show very similar results.
The results of the 22 trials that directly compared triptans show the same overall
pattern. We received no data on frovatriptan, but publicly available data suggest
substantially lower efficacy. The major methodological issues involve the choice
of the primary endpoint, consistency over multiple attacks, how to evaluate headache
recurrence, use of placebo-subtracted proportions to control for across-study
differences, and the difference between tolerability and safety. In addition,
there are a number of methodological issues specific for direct comparator trials,
including encapsulation and patient selection. At marketed doses, all oral triptans
are effective and well tolerated. Differences among them are in general relatively
small, but clinically relevant for individual patients. Rizatriptan 10 mg, eletriptan
80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success.
Sumatriptan features the longest clinical experience and the widest range of formulations.
All triptans are contra-indicated in the presence of cardiovascular disease."
Tepper SJ, Rapoport AM, Sheftell FD.
of action of the 5-HT1B/1D receptor agonists.
"Recent studies of the pathophysiology of migraine
provide evidence that the headache phase is associated with multiple physiologic
actions. These actions include the release of vasoactive neuropeptides by the
trigeminovascular system, vasodilation of intracranial extracerebral vessels,
and increased nociceptive neurotransmission within the central trigeminocervical
complex. The 5-HT(1B/1D) receptor agonists, collectively known as triptans, are
a major advance in the treatment of migraine. The beneficial effects of the triptans
in patients with migraine are related to their multiple mechanisms of action at
sites implicated in the pathophysiology of migraine. These mechanisms are mediated
by 5-HT(1B/1D) receptors and include vasoconstriction of painfully dilated cerebral
blood vessels, inhibition of the release of vasoactive neuropeptides by trigeminal
nerves, and inhibition of nociceptive neurotransmission. The high affinity of
the triptans for 5-HT(1B/1D) receptors and their favorable pharmacologic properties
contribute to the beneficial effects of these drugs, including rapid onset of
action, effective relief of headache and associated symptoms, and low incidence
of adverse effects." [Abstract]
Almeida RM, Miczek KA.
Aggression escalated by social instigation
or by discontinuation of reinforcement ("frustration") in mice: inhibition
by anpirtoline: a 5-HT1B receptor agonist.
"Experiments with social instigation or the omission
of scheduled reinforcement show that serotonergic mechanisms may be involved in
escalated aggression in animals. 5-HT1B 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-HT1B 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-HT1B/1D receptor antagonist GR127935 (10 mg/kg). Anpirtoline,
like other 5-HT1B agonists (CP-94,253, zolmitriptan), decreased both instigated
and frustration-heightened aggression, while motor behavior was unaffected. The
aggression-inhibiting effects of anpirtoline were blocked by pretreatment with
GR127935. The current results indicate that the 5-HT(1B) receptor is critically
involved in the modulation of escalated aggression." [Abstract]
AM, Trillat AC, Malagie I, David D, Hascoet M, Colombel MC, Jolliet P, Jacquot
C, Hen R, Bourin M.
[5-HT1B serotonin receptors and antidepressant
effects of selective serotonin reuptake inhibitors ]
R Acad Sci III 2001 May;324(5):433-41
"Furthermore, we demonstrate that
SSRIs decrease immobility in the forced swimming test; this effect is absent in
5-HT1B knockout mice and blocked by GR 127935 in wild-type suggesting therefore
that activation of 5-HT1B receptors mediate the antidepressant-like effects of
SSRIs. Taken together these data demonstrate that 5-HT1B autoreceptors appear
to limit the effects of SSRI on dialysate 5-HT levels particularly in the hippocampus
while presynaptic 5-HT1B heteroreceptors are likely to be required for the antidepressant
activity of SSRIs." [Abstract]
Mendez, Jorge, Kadia, Tapan M., Somayazula, Ravi K.,
El-Badawi, Khaled I., Cowen, Daniel S.
Differential Coupling of
Serotonin 5-HT1A and 5-HT1B Receptors to Activation of ERK2 and Inhibition of
Adenylyl Cyclase in Transfected CHO Cells.
J Neurochem 1999
"In summary, there are accumulating data demonstrating that
Gi-coupled receptors are not identical but exhibit functional differences." [Abstract]
Carr, David B., Cooper, Donald C., Ulrich, Sasha
L., Spruston, Nelson, Surmeier, D. James
Serotonin Receptor Activation
Inhibits Sodium Current and Dendritic Excitability in Prefrontal Cortex via a
Protein Kinase C-Dependent Mechanism
J. Neurosci. 2002
"Although 5-HT2a,c receptor activation did not affect
somatic action potentials of layer V pyramidal neurons in PFC slices, it did reduce
the amplitude of action potentials backpropagating into the apical dendrite. These
findings show that 5-HT2a,c receptor activation reduces dendritic excitability
and may negatively modulate activity-dependent dendritic synaptic plasticity."
Alban, Goaillard, Jean-Marc, Cases, Olivier, Lebrand, Cecile, Gaspar, Patricia,
Activity-Dependent Presynaptic Effect of Serotonin
1B Receptors on the Somatosensory Thalamocortical Transmission in Neonatal Mice
J. Neurosci. 2002 22: 886-900 [Abstract]
Berg, KA, Maayani, S, Clarke, WP
receptor activation inhibits 5- hydroxytryptamine1B-like receptor function via
arachidonic acid metabolism
Mol Pharmacol 1996 50: 1017-1023
"Activation of 5-HT2C receptors with 5-HT or (+/-)-1-(2,5-dimethoxy-4-
iodophenyl)-2-aminopropane increased release of arachidonic acid via a phospholipase
A2 (PLA2)-dependent mechanism." [Abstract]
Hsu, Eugenia H., Lochan, Anthony C., Cowen, Daniel
Activation of Akt1 by Human 5-Hydroxytryptamine (Serotonin)1B
Receptors Is Sensitive to Inhibitors of MEK
Exp Ther 2001 298: 825-832 [Full
Hain, Heather S., Belknap, John K., Mogil,
Pharmacogenetic Evidence for the Involvement of 5-Hydroxytryptamine
(Serotonin)-1B Receptors in the Mediation of Morphine Antinociceptive Sensitivity
J Pharmacol Exp Ther 1999 291: 444-449 [Full
Jeffrey S. Mogil
mediation of individual differences in sensitivity to pain and its inhibition
PNAS 96: 7744-7751, July 6, 1999. [Full
Crabbe, John C., Manzoni, Olivier J., Morikawa,
Hitoshi, Williams, John T.
Regulation of central synaptic transmission
by 5-HT1B auto- and heteroreceptors.
, 58(6):1271-1278 2000
"In the ventral midbrain, 5-HT1B receptor-dependent
inhibition of gamma-aminobutyric acidB IPSPs in dopamine neurons was present in
wild-type animals and absent in knockout animals. Similar results were obtained
in the nucleus accumbens measuring glutamate-mediated excitatory postsynaptic
currents in medium spiny neurons." [Full Text]
Muramatsu M, Lapiz MD, Tanaka E, Grenhoff J.
Serotonin inhibits synaptic glutamate currents in rat nucleus accumbens neurons
via presynaptic 5-HT1B receptors.
Eur J Neurosci 1998 Jul;10(7):2371-9
Nicolas, Franck, Louis, Langlois, Xavier, Hamon, Michel, Darmon, Michele
Dominant Role of the Cytosolic C-Terminal Domain of the Rat 5-HT1B Receptor
in Axonal-Apical Targeting
J. Neurosci. 2000 20: 9111-9118
"Therefore, the short tail of the 5-HT1BR presents an apical targeting
signal that can also act as an axonal targeting signal. In addition, a domain
within the third intracytoplasmic loop of the 5-HT1BR, responsible for its Golgi
sequestration in LLC-PK1 cells, appeared to act as another axonal targeting signal
in hippocampal neurons." [Full
Garabette, M. L., Martin, K. F., Redfern,
Circadian variation in the activity of the 5-HT1B autoreceptor
in the region of the suprachiasmatic nucleus, measured by microdialysis in the
conscious freely-moving rat
Br. J. Pharmacol. 2000 131:
Gary E., Smith, Bret N., Belenky, Michael, Rea, Michael A., Dudek, F. Edward,
Sollars, Patricia J.
5-HT1B Receptor-Mediated Presynaptic Inhibition
of Retinal Input to the Suprachiasmatic Nucleus
1999 19: 4034-4045 [Full
Pickard, Gary E., Weber, E. Todd, Scott,
Paul A., Riberdy, Anne F., Rea, Michael A.
5HT1B Receptor Agonists
Inhibit Light-Induced Phase Shifts of Behavioral Circadian Rhythms and Expression
of the Immediate-Early Gene c-fos in the Suprachiasmatic Nucleus
J. Neurosci. 1996 16: 8208-8220 [Full
Rea, M. A.
of Circadian Rhythms in Rodents
, 15(5):395-424 1998
"In addition, serotonin appears to regulate the response of the SCN
circadian clock to light through postsynaptic 5-HT1A or 5-ht7 receptors, as well
as presynaptic 5-HT1B heteroreceptors on RHT [retinohypothalamic tract] terminals."
Deborah A., Hen, Rene, Lucki, Irwin
Genetic Regulation of Extracellular
Serotonin by 5-Hydroxytryptamine1A and 5-Hydroxytryptamine1B Autoreceptors
in Different Brain Regions of the Mouse
J Pharmacol Exp
Ther 2001 298: 1083-1091 [Full
Knobelman, Deborah A., Hen, Rene, Blendy,
Julie A., Lucki, Irwin
Regional Patterns of Compensation following
Genetic Deletion of Either 5-Hydroxytryptamine1A or 5-Hydroxytryptamine1B Receptor
in the Mouse
J Pharmacol Exp Ther 2001 298: 1092-1100
"Based on their altered response to microdialysis studies, we propose that
striatal 5-HT1B receptors increase their sensitivity in 5-HT1A receptor knockout
mice and MR [median raphe nucleus] 5-HT1A receptors are desensitized in 5-HT1B
receptor knockout mice." [Full
R Jackisch, A Haaf, H Jeltsch, C Lazarus,
C Kelche, J C Cassel
Modulation of 5-hydroxytryptamine release
in hippocampal slices of rats: effects of fimbria-fornix lesions on 5-HT1B-autoreceptor
and alpha2-heteroreceptor function
Brain Res Bull. 1999 Jan 1;48(1):49-59. [Abstract]
Lynette C., Gould, Georgianna G., Teicher, Susan D., Gerhardt, Greg A., Frazer,
5-HT1B Receptor-Mediated Regulation of Serotonin Clearance
in Rat Hippocampus In Vivo
J Neurochem 2000 75: 2113-2122
"Using high-speed chronoamperometry, we have demonstrated that local application
of 5-HT1B antagonists into the CA3 region of the hippocampus prolongs the clearance
of 5-HT from extracellular fluid (ECF). In the present study, we demonstrate that
the 5-HT1B antagonist cyanopindolol does not produce this effect by increasing
release of endogenous 5-HT or by directly binding to the 5-HTT. Dose-response
studies showed that the potency of cyanopindolol to inhibit clearance of 5-HT
was equivalent to that of the selective 5-HT reuptake inhibitor fluvoxamine. Local
application of the 5-HT1A antagonist WAY 100635 did not alter 5-HT clearance,
suggesting that the effect of cyanopindolol to prolong clearance is not via a
mechanism involving 5-HT1A receptors. Finally, the effect of low doses of cyanopindolol
and fluvoxamine to inhibit clearance of 5-HT from ECF was additive. These data
are consistent with the hypothesis that activation of terminal 5-HT1B autoreceptors
increases 5-HTT activity." [Abstract]
Daws LC, Gerhardt GA, Frazer A.
5-HT1B antagonists modulate clearance of extracellular serotonin in rat hippocampus.
Neurosci Lett. 1999 May 14;266(3):165-8.
"In vivo chronoamperometry was used to determine the effects of locally applied antagonists of the serotonin-1B (5-HT1B) receptor (cyanopindolol, 5-HT-moduline and methiothepin) on the clearance of 5-HT in the CA3 region of the dorsal hippocampus and the corpus callosum (a brain region devoid of serotonin transporters and 5-HT1B receptors) of the rat. When 5-HT was pressure ejected into these regions, reproducible signals were detected. In the CA3 region, local application of 5-HT1B antagonists decreased the rate of clearance of the serotonin signal comparably to the selective 5-HT uptake inhibitor (SSRI), fluvoxamine. By contrast, in the corpus callosum, none of the drugs altered the 5-HT signal. One interpretation of these data is that 5-HT1B receptors can modulate the activity of the 5-HT transporter." [Abstract]
Tamsin J.O., Hannon, Serina D., Redfern, Peter H., Martin, Keith F.
Diurnal variation in 5-HT1B autoreceptor function in the anterior hypothalamus
in vivo: effect of chronic antidepressant drug treatment
J. Pharmacol. 1999 126: 1777-1784
"Following treatment with either paroxetine
hydrochloride (10 mg kg-1 i.p.) or desipramine hydrochloride (10 mg kg-1 i.p.)
for 21 days the function of the terminal 5-HT1B autoreceptor was more markedly
attenuated at end-light." [Abstract]
QS , Yan SE
Serotonin-1B receptor-mediated inhibition of [(3)H]GABA
release from rat ventral tegmental area slices.
79(4): 914-22 2001 [Abstract]
Arthur J., Dalvi, Ashutosh, Page, Michelle E., Zimov-Levinson, Sarah, Hen, Rene,
Antidepressant-Like Behavioral Effects in 5-Hydroxytryptamine1A
and 5-Hydroxytryptamine1B Receptor Mutant Mice
Exp Ther 2001 298: 1101-1107 [Full
Trillat, AC, Malagie, I, Scearce, K, Pons,
D, Anmella, MC, Jacquot, C, Hen, R, Gardier, AM
Regulation of serotonin
release in the frontal cortex and ventral hippocampus of homozygous mice lacking
5-HT1B receptors: in vivo microdialysis studies.
1997 69: 2019-2025
"These data provide in vivo evidence that, in mice,
5-HT1B, but not 5-HT1D, autoreceptors inhibit 5-HT release at nerve terminals
located in the frontal cortex and ventral hippocampus." [Abstract]
H, Marsicano G, Lutz B.
Coexpression of the cannabinoid receptor
type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations
of the adult mouse forebrain.
"The cannabinoid receptor type 1 (CB1) displays unusual properties, including
the dual capacity to inhibit or stimulate adenylate cyclase and a brain density
considerably higher than the majority of G protein-coupled receptors. Together
with overlapping expression patterns of dopamine and serotonin receptors this
suggests a potential of CB1 to modulate the function of the dopamine and serotonin
system. Indeed, pharmacological studies provide evidence for cross-talks between
CB1 and receptors of these neurotransmitter systems. In trying to obtain further
insights into possible functional and/or structural interactions between CB1 and
the dopamine receptors and the serotonin receptors, we performed double-label
in situ hybridization at the cellular level on mouse forebrain sections by combining
a digoxigenin-labelled riboprobe for CB1 with 35S-labelled riboprobes for dopamine
receptors D1 and D2, and for serotonin receptors 5-HT1B and 5-HT3, respectively.
As a general rule, we found that CB1 colocalizes with D1, D2 and 5-HT1B only in
low-CB1-expressing cells which are principal projecting neurons, whereas CB1 coexpression
with 5-HT3 was also observed in high-CB1-expressing cells which are considered
to be mostly GABAergic. In striatum and olfactory tubercle, CB1 is coexpressed
to a high extent with D1, D2 and 5-HT1B. Throughout the hippocampal formation,
CB1 is coexpressed with D2, 5-HT1B and 5-HT3. In the neocortex, coexpression was
detected only with 5-HT1B and 5-HT3. In summary a distinct pattern is emerging
for the cannabinoid system with regard to its colocalization with dopamine and
serotonin receptors and, therefore, it is likely that different mechanisms underlie
its cross-talk with these neurotransmitter systems." [Abstract]
Massot, O, Rousselle, JC, Fillion, MP, Grimaldi,
B, Cloez-Tayarani, I, Fugelli, A, Prudhomme, N, Seguin, L, Rousseau, B, Plantefol,
M, Hen, R, Fillion, G
5-hydroxytryptamine-moduline, a new endogenous
cerebral peptide, controls the serotonergic activity via its specific interaction
with 5- hydroxytryptamine1B/1D receptors
1996 50: 752-762
"The interaction of 5-HT-moduline with the 5-HT1B/1D
receptor corresponds to a decrease in the functional activity of the receptor
(i.e., a decrease in the inhibitory effect of a 5-HT1B agonist on the evoked release
of [3H]5-HT from synaptosomal preparation). It was also shown that 5-HT- moduline
possess an in vivo effect in the social interaction test in mouse. Finally, it
was demonstrated that 5-HT-moduline was released from brain synaptosomal preparation
by a K+/Ca(2+)-dependent mechanism. In conclusion, 5-HT-moduline is a novel endogenous
peptide regulating the serotonergic activity via a direct action at presynaptic
5-HT receptor. It may play an important role in the physiological mechanisms involving
the serotonergic system, particularly in mechanisms corresponding to the elaboration
of an appropriate response of the central nervous system to a given stimulus."
B , Fillion G
5-HT-moduline controls serotonergic activity: implication
in neuroimmune reciprocal regulation mechanisms
60(1): 1-12 2000
"In particular, the receptors located on immunocompetent
cells control their activity and are themselves regulated by 5-HT-moduline likely
originating from adrenal medulla and released after acute stress. The serotonergic
system appears to play a major role in the reciprocal signalling existing between
the neuronal and the immune system. The participation of 5-HT-moduline is likely
in physiological functions as well as in pathological disorders affecting central
and peripheral activities." [Abstract]
M, Kenis G, Bosmans E.
THE NEGATIVE IMMUNOREGULATORY EFFECTS OF
SEROTONIN (5-HT) MODULINE, AN ENDOGENOUS 5-HT1B RECEPTOR ANTAGONIST WITH ANTI-ANXIETY
Cytokine 2002 Nov;19(6):308-311
Serotonin (5-HT) has negative immunoregulatory effects by reducing the interferon-gamma
(IFNgamma)/interleukin-10 (IL-10) production ratio by stimulated immune cells.
Leukocytes have functional 5-HT1B receptors. 5-HT moduline, an endogenous 5-HT1B
receptor antagonist, may antagonize the 5-HT1B agonist-induced proliferation of
immune cells. AIMS: To examine the effects of 5-HT moduline on the stimulated
production of IFNgamma, tumor necrosis factor alpha (TNFalpha) and IL-10. RESULTS:
5-HT moduline, 10(-6) M and 10(-5)M, significantly reduced the production of IFNgamma
and the IFNgamma/IL-10 ratio. 5-HT moduline 10(-5)M significantly reduced the
production of TNFalpha. The combination of 5-HT, 15&mgr;g/mL, with 5-HT moduline,
10(-6)M and 10(-5)M, further decreases the IFNgamma/IL-10 production ratio. INTERPRETATION:
5-HT moduline has negative immunoregulatory effects." [Abstract]
Cloëz-Tayarani, Ana Cardona, Jean-Claude Rousselle, Olivier Massot, Lena
Edelman, and Gilles Fillion
Autoradiographic characterization of
[3H]-5-HT-moduline binding sites in rodent brain and their relationship to 5-HT1B
PNAS 94: 9899-9904.
"The highest binding
densities were found in septum, olfactory system, frontoparietal, and cingulate
cortices. In septum, the strongest signals were observed in lateral septal nuclei,
horizontal limb diagonal band, whereas in olfactory system, the primary olfactory
cortex and the anterior olfactory nucleus were the predominant labeled structures.
Other areas with significant [3H]-5-HT-moduline binding sites included the amygdala,
hypothalamus, frontal, entorhinal and cingulate cortices, accumbens nucleus, ventral
pallidum, dentate gyrus of hippocampus, superficial gray layer of the superior
Rousselle JC, Plantefol M, Fillion MP, Massot O, Pauwels PJ, Fillion G.
Specific interaction of 5-HT-moduline with human 5-HT1b as well as 5-HT1d receptors expressed in transfected cultured cells.
Naunyn Schmiedebergs Arch Pharmacol. 1998 Sep;358(3):279-86. [Abstract]
G., Lopez-Garcia, J.A.
5-HT1B but not 5-HT6 or 5-HT7 receptors mediate
depression of spinal nociceptive reflexes in vitro
J. Pharmacol. 2002 135: 935-942
"The data suggest an important contribution
of 5-HT1B receptors to the inhibition of spinal C-fibre mediated nociceptive reflexes
but no experimental support was found for the intervention of 5-HT2, 5-HT6 or
5-HT7 receptors in this in vitro model." [Abstract]
Mathieu, Rousselle, Jean Claude, Massot, Olivier, Bernardi, Elizabeth, Schoofs,
Alain Rene, Pourrias, Bernard, Ollivier, Roland, Fillion, Gilles
Requirements of 5-Hydroxytryptamine-Moduline Analogues to Interact with the 5-Hydroxytryptamine1B
J Neurochem 1999 73: 2617-2620
work focuses on the ability of 5-hydroxytryptamine-moduline analogues to recognize
the high- and low-affinity sites for 5-hydroxytryptamine-moduline. The results
obtained show that the two conformers of the 5-hydroxytryptamine1B receptor have
similar but not identical binding pockets for 5-hydroxytryptamine-moduline." [Abstract]
of human T lymphoblastic cells induced by 5-HT1B receptors activation is regulated
C R Acad Sci III, 324(4): 365-72 2001
"The purpose of the herein reported experiments was to investigate whether
serotonin could regulate the proliferation of a human T lymphoblastic leukemia
cell line (CCRF-CEM cells) and to characterize the 5-HT receptor(s) involved in
this phenomenon using a pharmacological approach. The herein presented results
show that serotonin alone stimulated the proliferation of CCRF-CEM cells and that
this effect could be mimicked by two 5-HT1B/1D receptor agonists (L-694,247 and
GR 46611)." [Abstract]
Rousselle_J_C, Bernardi_E, Schoofs_A_R, Pourrias_B, Fillion_G
activity in mammalian brain membranes cleaves 5-hydroxytryptamine-moduline into
European journal of pharmacology , 376(1-2):109-117
Bentue-Ferrer D, Reymann JM, Rousselle JC, Massot O, Bourin M, Allain H, Fillion G.
5-HT-moduline, a 5-HT(1B/1D) receptor endogenous modulator, interacts with dopamine release measured in vivo by microdialysis.
Eur J Pharmacol. 1998 Oct 2;358(2):129-37. [Abstract]
WHALE, RICHARD, CLIFFORD, ELIZABETH M., BHAGWAGAR,
ZUBIN, COWEN, PHILIP. J.
Decreased sensitivity of 5-HT1D receptors
in melancholic depression
Br J Psychiatry 2001 178: 454-457
F;deCastro, RM;Seguin, L;CloezTayarani, I;Monneret, V;Drieu, K;Fillion, G
Effects of stress on the functional properties of pre- and postsynaptic 5-HT1B
receptors in the rat brain
EUROPEAN JOURNAL OF PHARMACOLOGY
294: (2-3) 531-540 DEC 29 1995
"Similarly, the responsiveness of 5-HT1B
receptors inhibiting the release of [H-3]acetylcholine (presynaptic 5-HT1B heteroreceptors),
was reduced by restraint. These effects were observed in the hippocampus, but
using the inhibitory effect of CP-93,129 on forskolin-stimulated adenylyl cyclase
activity as an index of 5-HT1B receptor function, it could be shown that the 5-HT1B
receptors located in the substantia nigra are also desensitized by stress."
F, Manhaes de Castro R, Fillion G
Effect of chronic antidepressant
treatment on 5-HT1B presynaptic heteroreceptors inhibiting acetylcholine release.
Neuropharmacology, 33(1): 77-81 1994
suggest that chronic antidepressant treatment desensitizes 5-HT1B presynaptic
heteroreceptors through a mechanism which seems to be independent of the synaptic
availability of 5-HT." [Abstract]
Ariel R., Reader, Tomas A., Hen, Rene, Riad, Mustapha, Descarries, Laurent
Regional changes in density of serotonin transporter in the brain of 5-HT1A
and 5-HT1B knockout mice, and of serotonin innervation in the 5-HT1B knockout.
J Neurochem 2001 78: 619-630 [Abstract]
Eugenia H., Lochan, Anthony C., Cowen, Daniel S.
Activation of Akt1
by Human 5-Hydroxytryptamine (Serotonin)1B Receptors Is Sensitive to Inhibitors
J Pharmacol Exp Ther 2001 298: 825-832 [Full
Lione, Angelique M., Errico, Monica, Lin,
Stanley L., Cowen, Daniel S.
Activation of Extracellular Signal-Regulated
Kinase (ERK) and Akt by Human Serotonin 5-HT1B Receptors in Transfected BE(2)-C
Neuroblastoma Cells Is Inhibited by RGS4.
J Neurochem 2000
75: 934-938 [Abstract]
Newman-Tancredi, Adrian, Audinot, Valerie,
Moreira, Celia, Verriele, Laurence, Millan, Mark J.
and Constitutive Activity as Functional Correlates of Serotonin h5-HT1B Receptor/G-Protein
Mol Pharmacol 2000 58: 1042-1049
key findings of the present study are that an augmentation of h5-HT1B R:G [receptor/G-protein]
stoichiometry is associated with changes in ligand-binding affinities, increased
relative efficacies of partial agonists, and, notably, increased constitutive
G-protein activation and negative efficacy of inverse agonists at h5-HT1B receptors."
Ariel R., Reader, Tomas A., Hen, Rene, Riad, Mustapha, Descarries, Laurent
Altered Serotonin and Dopamine Metabolism in the CNS of Serotonin 5-HT1A or
5-HT1B Receptor Knockout Mice.
J Neurochem 2000 75: 2415-2426 [Abstract]
Gabriela, Lopez-Rubalcava, Carolina, Hen, Rene, Fernandez-Guasti, Alonso
Participation of 5-HT1B receptors in the inhibitory actions of serotonin on
masculine sexual behaviour of mice: pharmacological analysis in 5-HT1B receptor
Br. J. Pharmacol. 2002 136: 1127-1134 [Abstract]
F., Boulenguez, P., Semont, A., Hery, M., Pesce, G., Becquet, D., Faudon, M.,
Deprez, P., Fache, M.-P.
Identification and Role of Serotonin 5-HT1A
and 5-HT1B Receptors in Primary Cultures of Rat Embryonic Rostral Raphe Nucleus
J Neurochem 1999 72: 1791-1801 [Abstract]
Salichon, Nathalie, Gaspar, Patricia, Upton,
A. Louise, Picaud, Sandrine, Hanoun, Naima, Hamon, Michel, De Maeyer, Edward,
Murphy, Dennis L., Mossner, Rainald, Lesch, Klaus Peter, Hen, Rene, Seif, Isabelle
Excessive Activation of Serotonin (5-HT) 1B Receptors Disrupts the Formation
of Sensory Maps in Monoamine Oxidase A and 5-HT Transporter Knock-Out Mice
J. Neurosci. 2001 21: 884-896
"This demonstrates that
the 5-HT1B receptor is a key factor in abnormal segregation of sensory projections
and suggests that serotonergic drugs represent a risk for the development of these
projections. We also found that the 5-HT1B receptor has an adverse developmental
impact on beam-walking behavior in MAOA knock-outs. Finally, because the 5-HT1B
receptor inhibits glutamate release, our results suggest that visual and somatosensory
projections must release glutamate for proper segregation." [Full
Parsons, Loren H., Weiss, Friedbert,
Koob, George F.
Serotonin1B Receptor Stimulation Enhances Cocaine
J. Neurosci. 1998 18: 10078-10089 [Full
Lucas, Jose J., Segu, Louis, Hen, Rene
5-Hydroxytryptamine1B Receptors Modulate the Effect of Cocaine on c-fos Expression:
Converging Evidence Using 5-Hydroxytryptamine1B Knockout Mice and the 5-Hydroxytryptamine1B/1D
Mol Pharmacol 1997 51: 755-763 [Full
Hjorth S, Bengtsson HJ, Kullberg A, Carlzon
D, Peilot H, Auerbach SB.
Serotonin autoreceptor function and antidepressant
J Psychopharmacol 2000 Jun;14(2):177-85
"In particular, emerging data suggest that somatodendritic 5-HT1A autoreceptor-
and nerve terminal 5-HT1B autoreceptor-mediated feedback may be relatively more
important in the control of 5-HT output in dorsal raphe-frontal cortex and median
raphe-dorsal hippocampus systems, respectively." [Abstract]
AC, Malagie I, Bourin M, Jacquot C, Hen R, Gardier AM.
mice deficient in serotonin 5-HT1B receptor and antidepressant effect of selective
serotonin reuptake inhibitors]
C R Seances Soc Biol Fil
"Using microdialysis in awake 129/Sv mice, we show
that the absence of the 5-HT1B receptor in mutant mice (KO 1B -/-) potentiated
the effect of paroxetine on extracellular 5-HT levels in the ventral hippocampus,
but not in the frontal cortex compared to wild-type mice (WT). Furthermore, using
the forced swimming test, we demonstrate that SSRIs decreased immobility of WT
mice, and this effect is absent in KO 1B -/- mice showing therefore that activation
of 5-HT1B receptors mediate the antidepressant-like effects of SSRIs. Taken together
these findings suggest that 5-HT1B autoreceptors limit the effects of SSRI particularly
in the hippocampus while postsynaptic 5-HT1B receptors are required for the antidepressant
activity of SSRIs." [Abstract]
A, Laporte AM, Chastanet M, Hen R, Hamon M, Adrien J.
5-HT1B receptors control the firing of serotoninergic neurons in the dorsal raphe
nucleus of the mouse: studies in 5-HT1B knock-out mice.
J Neurosci 1999 Nov;11(11):3823-31 [Abstract]
C, Ho, M, Price, GW, Jones, BJ, Stamford, JA
(+)-WAY 100135, a partial
agonist, at native and recombinant 5-HT1B/1D receptors
J. Pharmacol. 1997 121: 737-742 [Abstract]
Gobert A, Rivet JM, Cistarelli L, Millan MJ.
Potentiation of the fluoxetine-induced increase in dialysate levels of serotonin
(5-HT) in the frontal cortex of freely moving rats by combined blockade of 5-HT1A
and 5-HT1B receptors with WAY 100,635 and GR 127,935.
Neurochem 1997 Mar;68(3):1159-63 [Abstract]
C, Magnusson T, Larsson LG, Yu H, Hallbus M, Magnusson O, Ross SB.
Synergism between 5-HT1B/1D and 5-HT1A receptor antagonists on turnover and
release of 5-HT in guinea-pig brain in vivo.
Arch Pharmacol 1999 Feb;359(2):110-6 [Abstract]
GJ, Frolich D, Likungu J, Gothert M.
Inhibition of noradrenaline
release via presynaptic 5-HT1D alpha receptors in human atrium.
Naunyn Schmiedebergs Arch Pharmacol 1996 Feb;353(3):272-80 [Abstract]
Isabelle, Trillat, Anne-Cecile, Bourin, Michel, Jacquot, Christian, Hen, Rene,
Gardier, Alain M.
5-HT1B Autoreceptors limit the effects of selective
serotonin re-uptake inhibitors in mouse hippocampus and frontal cortex
J Neurochem 2001 76: 865-871 [Abstract]
SAUDOU, F;AMARA, DA;DIERICH, A;LEMEUR, M;RAMBOZ,
S;SEGU, L;BUHOT, MC;HEN, R
Enhanced aggressive behavior in mice lacking 5-HT1B receptor.
SCIENCE 265: (5180) 1875-1878 SEP
"Moreover, when confronted with an intruder, mutant mice attacked
the intruder faster and more intensely than did wild-type mice, suggesting the
participation of 5-HT1B receptors in aggressive behavior." [Abstract]
Hala, Fillion, Gilles
Differential sensitivity of 5-HT1B auto and
NAUNYN-SCHMIEDEBURG'S ARCHIVES OF PHARMACOLOGY
, 360(4):382-390. 1999 [Abstract]
K, Viswanathan SS, Hen R.
Locomotor response to MDMA is attenuated
in knockout mice lacking the 5-HT1B receptor.
(Berl) 1999 Jan;141(2):154-61 [Abstract]
Craig F., Melloni Jr, Richard H., Koppel, Gary, Perry, Kenneth W., Fuller, Ray
W., Delville, Yvon
Vasopressin/Serotonin Interactions in the Anterior
Hypothalamus Control Aggressive Behavior in Golden Hamsters
Neurosci. 1997 17: 4331-4340
"Because postsynaptic 5-HT1B receptors seem
to be fundamental in the modulation of offensive aggression, it is reasonable
to postulate that 5-HT activates these receptors, making a neuron co-innervated
by AVP unresponsive to the excitatory effects of the neuropeptide." [Full
Callahan PM, Cunningham KA.
Modulation of the discriminative stimulus properties of cocaine: comparison
of the effects of fluoxetine with 5-HT1A and 5-HT1B receptor agonists.
Neuropharmacology 1997 Mar;36(3):373-81 [Abstract]
Mansari M, Blier P.
Functional characterization of 5-HT1D autoreceptors
on the modulation of 5-HT release in guinea-pig mesencephalic raphe, hippocampus
and frontal cortex.
Br J Pharmacol 1996 Jun;118(3):681-9
C, Francois-Bellan AM, Segu L, Becquet D, Hery M, Faudon M, Hery F.
Impairment of serotoninergic transmission is followed by adaptive changes in
5HT1B binding sites in the rat suprachiasmatic nucleus.
Res 1994 Nov 7;663(1):93-100 [Abstract]
A, Rodriguez-Manzo G.
Further evidence showing that the inhibitory
action of serotonin on rat masculine sexual behavior is mediated after the stimulation
of 5-HT1B receptors.
Pharmacol Biochem Behav 1992 Jul;42(3):529-33
M, Hascoet M.
Drug mechanisms in anxiety.
Opin Investig Drugs 2001 Feb;2(2):259-65 [Abstract]