Species differences in the pharmacology of terminal 5-HT autoreceptors in mammalian brain

Hoyer, Daniel; Middlemiss, Derek N.

doi:10.1016/0165-6147(89)90159-4

Cited by 326 publications

(130 citation statements)

References 21 publications

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Section: Knockout Of the 5-ht 1b Gene In Mice Results In Increased Agmentioning

confidence: 99%

“…The pattern of expression of this receptor is similar among mammalian species with a predominant expression in projections areas of raphe neurons as well as of striatal neurons (Boschert et al 1994). This receptor inhibits transmitter release from nerve terminals (Hoyer and Middlemiss 1989;Martin and Humphrey 1994).A common polymorphism at the human 5-HT 1B receptor locus (G861C) was identified by Hinc II restriction enzyme (Sidenberg et al 1993) and by SSCP and PCR-RFLP methods (Lappalainen et al 1995). An uncommon molecular variant with the substitution of a cysteine for a phenylalanine residue (F124C) has been detected in the human 5-HT 1B (5HT 1D ␤ ) receptor gene (Nöthen et al 1994).…”

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confidence: 99%

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Relationship of Psychopathology to the Human Serotonin1B Genotype and Receptor Binding Kinetics in Postmortem Brain Tissue

Huang¹,

Grailhe

Arango

et al. 1999

Neuropsychopharmacology

134

102

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Knockout of the 5-HT 1B gene in mice results in increased aggression, as well as alcohol and cocaine consumption. Given the clinical association of aggression, suicide, alcoholism, and substance abuse, we studied relationship of psychopathology to the human 5-HT 1B receptor gene (N ϭ 178) and postmortem human 5-HT 1B receptor binding (N ϭ96Several neuropsychiatric disorders such as mood disorders, substance abuse, or alcoholism have been associated with dysfunctions of the central serotonergic system (Coppen 1972;Goodwin and Post 1983;Ballenger et al. 1979;Virkkunen et al. 1994). The risk for suicidal behavior and aggressive acts has been suggested to be related to a common underlying predisposition to impulsive behavior that is modulated by serotonergic activity (Mann 1998). In rodents and primates, aggressiveness is increased after inhibition of serotonin synthesis or in association with lower serotonergic activity (Vergnes et al. 1986;Molina et al. 1987;Higley et al. 1992). Both suicidal acts and aggression have a genetic contribution in terms of cause or diathesis that is independent of the heritability of major psychiatric disorders (Brent et al. Received October 15, 1998; revised February 15, 1999; accepted February 25, 1999. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 21 , NO . 2 Psychopathology and Human 5-HT 1B Binding and Genotype 239 1996;Roy 1986;Roy et al. 1991;Schulsinger et al. 1979). The mechanism whereby genetics can affect aggressive and suicidal behavior is not known. The serotonergic system is one possibility because serotonergic activity is under substantial genetic control (Ishikawa et al. 1989;Higley et al. 1992;van Harten 1993). Patients at risk for suicidal acts not only have an increased level of lifetime aggression (Mann and Arango 1998), but also an increased rate of alcoholism and substance abuse. Alcoholism and substance abuse may facilitate suicidal acts, or may share a common predisposing factor with suicide and aggression, such as lower serotonergic activity. Genetic factors play a role in alcoholism (Schuckit et al. 1985) and major depression (Gershon et al. 1989) but their precise nature is unknown. Again, the serotonergic system may play a role.Recently, aggressive behavior as well as increased alcohol and cocaine intake have been reported in 5-HT 1B receptor gene knockout mice (Saudou et al. 1994;Ramboz et al. 1996;Crabbe et al. 1996;Rocha et al. 1998). This set of observations raises the possibility that abnormalities in the 5-HT 1B receptor gene may contribute to human psychopathologies such as suicide, aggression, major depression, alcoholism, or substance abuse.Molecular cloning techniques have revealed the existence of two humans 5-HT 1D receptor subtypes: 5-HT 1D ␣ and 5-HT 1D ␤ (Hamblin and Metcalf 1991;Demchyshyn et al. 1992;Weinshank et al. 1992;Levy et al. 1992). The mouse 5-HT 1B receptor is the homologue of the human 5-HT 1D ␤ . We have adopted the recommendation that the human 5-HT 1D ␤ receptor be renamed human 5-HT 1B (h5-HT 1B ) receptor (for a review see H...

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Section: Knockout Of the 5-ht 1b Gene In Mice Results In Increased Agmentioning

confidence: 99%

mentioning

confidence: 99%

Relationship of Psychopathology to the Human Serotonin1B Genotype and Receptor Binding Kinetics in Postmortem Brain Tissue

Huang¹,

Grailhe

Arango

et al. 1999

Neuropsychopharmacology

134

102

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“…The 5-HT 1A receptor is also found postsynaptically in brain nuclei receiving 5-HT axon projections, such as the hippocampus [21]. The 5-HT 1B receptor in the rat is found on presynaptic serotonergic terminals in many brain areas including the raphe and hippocampus and inhibits the synthesis and release of 5-HT from axon terminals [22]. However, the large majority of 5-HT 1B receptors are located on presynaptic terminals of non-serotonergic neurons throughout the CNS where they regulate the release of several different neurotransmitters from axon terminals [6].…”

Section: Introductionmentioning

confidence: 99%

Corticosteroids regulate 5-HT1A but not 5-HT1B receptor mRNA in rat hippocampus

Neumaier

Sexton

Hamblin

et al. 2000

Molecular Brain Research

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The role of mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) in the regulation of serotonin receptors has not been clearly delineated. There is no consensus regarding the regulation of 5-HT 1A receptors, and corticosteroid regulation of 5-HT 1B mRNA has not been previously studied. We compared the effects of long-term (two week) adrenalectomy (no MR or GR activation) and several hormone replacement protocols designed to stimulate MR selectively (ALDO), MR and GR (HCT), and continuous MR with cyclical GR activation (SHAM adrenalectomy). 5-HT 1A and 5-HT 1B mRNAs were measured by in situ hybridization in hippocampus and raphe nuclei. None of the experimental manipulations altered 5-HT 1B mRNA levels in the hippocampus or dorsal raphe, and also had no effect on 5-HT 1A mRNA in dorsal or median raphe. However, 5-HT 1A mRNA levels were regulated in a complex manner in the different subfields of hippocampus. We conclude that both MR and GR play an integrated role in regulating 5-HT 1A mRNA levels in hippocampus while having no effect on 5-HT 1B mRNA levels under these conditions.

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“…3 tors have a very similar pharmacology, but can be disSeven classes of 5-HT (5-hydroxytryptamine, tinguished using ketanserin and ritanserin. 14 [ 125 I]GTI, serotonin) receptors are recognised; 5-HT [1][2][3][4] [5][6][7] were ident-HT 1D receptors, 10,11,[15][16][17] but do not distinguish the two ified by molecular biology and are less well characterforms of the receptor. The 5-HT 1D␤ receptor appears to ised.…”

Section: Introductionmentioning

confidence: 99%

“…The 5-HT 1D receptor is of potential selective pharmacological blockade to examine 5-HT 1D interest because it functions as a nerve terminal autoreand 5-HT 1E/1F receptors (see Methods) in a group of ceptor, regulating the release of 5-HT. 7,8 To date only suicides, restricted to those with a firm retrospective one study has examined 5-HT 1D receptors in relation diagnosis of depression. We have studied separately to depression.…”

mentioning

confidence: 99%

5-HT1D and 5-HT1E/1F binding sites in depressed suicides: increased 5-HT1D binding in globus pallidus but not cortex

1997

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5-HTThe 5-HT 1B receptor in the rat and mouse tors. 18,19 In human frontal cortex these receptors is the species homologue of the 5-HT 1D␤ receptor in account for over 40% of the total 5-HT 1 receptors. 20 humans.They have not been studied to date in relation to Studies of the possible involvement of 5-HT 1 recepdepression. tors in depression have been largely limited to the 5-In the present study we have used [ 3 H]5-HT with HT 1A receptor. The 5-HT 1D receptor is of potential selective pharmacological blockade to examine 5-HT 1D interest because it functions as a nerve terminal autoreand 5-HT 1E/1F receptors (see Methods) in a group of ceptor, regulating the release of 5-HT. 7,8 To date only suicides, restricted to those with a firm retrospective one study has examined 5-HT 1D receptors in relation diagnosis of depression. We have studied separately to depression. Arranz et al 9 measured 5-HT 1D receptor those subjects who were free of antidepressants for at binding in frontal cortex of suicides. Although they least 3 months prior to death, and those in whom the found no significant difference overall compared to prescription of antidepressant drugs was clearly documatched controls, they found lower numbers of 5-HT 1D mented. Four brain regions were studied -frontal and parietal cortex, putamen and globus pallidus. We chose frontal cortex as this region is implicated in depression

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Species differences in the pharmacology of terminal 5-HT autoreceptors in mammalian brain

Cited by 326 publications

References 21 publications

Relationship of Psychopathology to the Human Serotonin1B Genotype and Receptor Binding Kinetics in Postmortem Brain Tissue

Relationship of Psychopathology to the Human Serotonin1B Genotype and Receptor Binding Kinetics in Postmortem Brain Tissue

Corticosteroids regulate 5-HT1A but not 5-HT1B receptor mRNA in rat hippocampus

5-HT1D and 5-HT1E/1F binding sites in depressed suicides: increased 5-HT1D binding in globus pallidus but not cortex

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