Localization of 5-HT2A receptors on dopamine cells in subnuclei of the midbrain A10 cell group

Nocjar, Christine; Roth, Bryan L.; Pehek, Elizabeth A.

doi:10.1016/s0306-4522(01)00593-0

Cited by 153 publications

(102 citation statements)

References 75 publications

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“…Employing immunohistochemistry with confocal microscopy, we have recently demonstrated that some of these receptors are colocalized with TH, indicating that they are on DA neurons in the VTA (Nocjar et al, 2002). This is in agreement with a previous electron microscopy study (Doherty and Pickel, 2000).…”

Section: -Ht2asupporting

confidence: 92%

“…However, it was blocked by ketanserin, which displays some selectivity for the 5-HT2A (average K i = 4.35 nM) versus the 5-HT2C (average K i = 92.43 nM) receptor (Psychoactive Drug Screening Program (PDSP): http://pdsp.cwru.edu/pdsp.htm). This work agrees with our findings that 5-HT2A receptors are localized directly on DA cells in the VTA (Nocjar et al, 2002). Pessia and colleagues (1994) further determined that 5-HT either depolarized or hyperpolarized presumed GABAergic neurons in the VTA.…”

Section: Mesolimbic Pathwaysupporting

confidence: 92%

“…As previously mentioned, we have shown that 5-HT2A receptors are localized on a subset of DA cells in the VTA (Nocjar et al, 2002). A physiological role for these receptors is largely unknown.…”

Section: Mesocortical Pathwaymentioning

confidence: 64%

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Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

518

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: -Ht2asupporting

confidence: 92%

Section: Mesolimbic Pathwaysupporting

confidence: 92%

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Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

518

311

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“…This potentiation may also result from the actions of drugs on DA cells in the VTA. We have shown that many VTA DA neurons express 5-HT2A receptors (Nocjar et al, 2002). It is clear from the present work that selective antagonism of cortical 5-HT2A receptors does not increase basal DA efflux but, in fact, blocks evoked DA release.…”

Section: Discussionsupporting

confidence: 50%

“…Both the mPFC and VTA are innervated by serotonergic neurons originating in the dorsal raphe (Azmitia and Segal, 1978;Beart and McDonald, 1982). Immunohistochemical studies indicate the presence of 5-HT2A receptors in both the PFC (Willins et al, 1997;Jakab and Goldman-Rakic, 1998;Miner et al, 2003) and VTA (Doherty and Pickel, 2000;Nocjar et al, 2002) where they could, at least in theory, modulate DA neuronal activity. In the mPFC, the vast majority of 5-HT2A receptors are localized to the apical dendrites of pyramidal cells and, to a lesser extent, GABAergic interneurons (Willins et al, 1997;Jakab and GoldmanRakic, 1998;Miner et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

Pehek

Nocjar

Roth

et al. 2005

Neuropsychopharmacol

168

104

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The mechanism(s) by which serotonin modulates dopamine release in the medial prefrontal cortex is not known, although studies suggest an involvement of 5-HT2 family receptors. We employed in vivo microdialysis and putatively selective 5-HT2A antagonists (M100907, MDL 11,939, SR46349B) to determine if 5-HT2A receptors are responsible for both drug-and stress-induced DA release in the medial prefrontal cortex. MDL 11,939 and SR46349B receptor-binding studies indicated, for the first time, that only MDL 11,939 had greater selectivity for the 5-HT2A vs the 5-HT2C receptor subtypes similar to M100907, and that both showed low or no affinity for non-5-HT2 receptors. Reverse dialysis with 5-HT2A antagonists had little or no effect on basal dopamine efflux. However, intracortical administration of MDL 11,939 or M100907 attenuated dopamine release induced by systemic administration of the 5-HT2 agonist DOI. Dual-probe microdialysis demonstrated that systemic DOI also increased glutamate concentrations in the ventral tegmental area (VTA). This was blocked by intracortical M100907. Cortical perfusion with M100907, or the atypical antipsychotic drug risperidone, but not the 5-HT2B/C ligand SB 206553, also decreased dopamine release induced physiologically by stress. These results indicate that stimulation of cortical 5-HT2A receptors increases the release of dopamine from the mesocortical system. They suggest that this effect may be mediated by increases in glutamate release from corticotegmental projections to the VTA. Additionally, they indicate that cortical 5-HT2A receptors modulate evoked dopamine release, such as that observed physiologically following mild stress. These findings may have implications for the pharmacological treatment of disorders resulting from or exacerbated by stress.

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Pharmacology

Bortolozzi

Daz-Mataix

Artigas

2007

Antidepressants, Antipsychotics, Anxiolytics

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Localization of 5-HT2A receptors on dopamine cells in subnuclei of the midbrain A10 cell group

Cited by 153 publications

References 75 publications

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

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