Distribution of serotonin 5-HT2A receptors in afferents of the rat striatum

Bubser, Michael; Backstrom, Jon R.; Sanders‐Bush, Elaine; Roth, Bryan L.; Deutch, Ariel Y.

doi:10.1002/1098-2396(20010315)39:4<297::aid-syn1012>3.0.co;2-q

Cited by 58 publications

(31 citation statements)

References 79 publications

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“…Corresponding to this, an immunohistochemical study employing retrograde labeling indicated that most 5-HT2A receptors are localized on striatal afferents with a low density on parvalbumin-containing interneurons (Bubser et al, 2001). These afferents arise mainly from the cortex and globus pallidus but not the SN.…”

Section: -Ht2amentioning

confidence: 87%

“…While receptor binding studies demonstrate relatively high levels of 5-HT2A receptors in the striatum, mRNA levels are very low (Bubser et al, 2001). Corresponding to this, an immunohistochemical study employing retrograde labeling indicated that most 5-HT2A receptors are localized on striatal afferents with a low density on parvalbumin-containing interneurons (Bubser et al, 2001).…”

Section: -Ht2amentioning

confidence: 99%

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Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

536

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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Section: -Ht2amentioning

confidence: 87%

Section: -Ht2amentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

536

311

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“…Secondly, most atypical antipsychotic drugs display a high affinity for the 5-HT 2A receptor in addition to the dopamine D 2 receptor (Meltzer, 1999;Scatton and Sanger, 2000). Thirdly, the 5-HT 2 subclass of receptors is densely expressed in many brain regions, including the striatum (Bubser et al, 2001) and prefrontal cortex (Jakab and Goldman-Rakic, 1998), and may modulate dopaminergic neurotransmission in limbic brain regions, such as the nucleus accumbens and prefrontal cortex (eg Lucas and Spampinato, 2000). Given the hypothetical role for a state of hyperdopaminergia in schizophrenia (Laruelle, 2000), the ability of these compounds to modify mesolimbic dopamine transmission highlights their importance as drugs with potential antipsychotic activity.…”

Section: Introductionmentioning

confidence: 99%

The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice

Barr

Lehmann-Masten

Paulus

et al. 2003

Neuropsychopharmacol

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A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT 2A receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/ kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT 2A receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.

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“…These discrepancies in receptor concentrations in the SN could be explained by the use in previous studies of some radioligands, such as [ 3 H]ketanserin, which has been shown to have a high affinity for nonserotonergic sites, as well as its known selectivity for the 5-HT 2 receptor family (Lopez-Gimenez et al, 1997). Finally, the presence of this receptor subtype in the GP of rat brain has been confirmed by recent immunohistochemistry data showing that about 70% of neurons expressing the 5-HT 2A receptor project to the striatum (Bubser et al, 2001). Neither 5-HT 2C mRNA nor receptor protein has been found in the GP or in the entopeduncular nucleus (EPN) while neurons showing labelling for this receptor have been found in both the SNc and the SNr.…”

Section: Substantia Nigra and Globus Pallidusmentioning

confidence: 82%

“…Early studies found high concentrations of [ 3 H]ketanserin binding in the SNc and the SNr in rats while only very low concentrations of this receptor have been shown in the GP (Pazos et al, , 1987b. Nevertheless, some recent immunohistochemistry and autoradiography studies found lower levels of 5-HT 2A receptors expressed in these areas (Cornea-He´bert et al, 1999;Lopez-Gimenez et al, 1999;Bubser et al, 2001). These discrepancies in receptor concentrations in the SN could be explained by the use in previous studies of some radioligands, such as [ 3 H]ketanserin, which has been shown to have a high affinity for nonserotonergic sites, as well as its known selectivity for the 5-HT 2 receptor family (Lopez-Gimenez et al, 1997).…”

Section: Substantia Nigra and Globus Pallidusmentioning

confidence: 99%

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

138

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Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

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Distribution of serotonin 5-HT2A receptors in afferents of the rat striatum

Cited by 58 publications

References 79 publications

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

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