Activation of a 5-HT3 receptor releases dopamine from rat striatal slice

Blandina, Patrizio; Goldfarb, Joseph; Green, Jack Peter

doi:10.1016/0014-2999(88)90528-6

Cited by 163 publications

(60 citation statements)

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“…Together with the recent demonstration of a binding site within brain tissue that displays a pharmacological profile consistent with that of a 5-HT3 receptor (Kilpatrick et al, 1987;Peroutka & Hamik, 1988;Barnes et al, 1988), the behavioural data suggest that functional 5-HT3 receptors may occur in the CNS. Consistent with this suggestion, 5-HT3 receptor activation has recently been reported to elicit inward currents from a population of voltageclamped rat hippocampal neurones in culture and also to modulate the release of dopamine from rat striatal slices (Blandina et al, 1988). Current knowledge of the molecular events that occur at 5-HT3 receptors is limited.…”

Section: Introductionmentioning

confidence: 87%

The properties of 5‐HT₃ receptors in clonal cell lines studied by patch‐clamp techniques

Lambert

Peters

Hales

et al. 1989

British J Pharmacology

131

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1 The characteristics of transmembrane currents evoked by 5-hydroxytryptamine (5-HT) in the neuroblastoma x Chinese hamster brain cell line On outside-out membrane patches excised from both NCB-20 and NlE-115 cells, 5-HT induced small inward currents which could not be clearly resolved into discrete single channel events. Such responses were: (i) reversibly antagonized by GR 38032F (1 nM) (ii) reversed in sign at 0 mV, and (iii) subject to desensitization. 6 Fluctuation analysis of inward currents evoked by 5-HT (1 M) in NlE-1 15 cells suggests that 5-HT gates a channel with a conductance of approximately 310fS. Such a relatively small conductance could readily explain why the response of outside-out membrane patches to 5-HT cannot at present be resolved into clear single channel events.

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Section: Introductionmentioning

confidence: 87%

The properties of 5‐HT₃ receptors in clonal cell lines studied by patch‐clamp techniques

Lambert

Peters

Hales

et al. 1989

British J Pharmacology

131

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“…5-HT3 agonism (using 2-Methyl-5-HT or 1-(m-chlorophenyl)biguanide (mCPBG)) has been shown to increase the release of endogenous DA from striatal slices (Blandina et al, 1988(Blandina et al, , 1989King et al, 1995;Richter et al, 1995) and potentiate K + -evoked release (Blandina et al, 1989). From these studies it was suggested that 5-HT acts at 5-HT3 receptors to facilitate DA release in the striatum.…”

Section: Nigrostriatal Pathwaymentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

526

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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“…The modulating effect of serotonin on striatal dopamine release is, however, controversial. For example, there is evidence that serotonin may inhibit (de Belleroche and Bradford 1980;Ennis et al 1981;Westfall and Tittermary 1982;Blandina et al 1988) as well as stimulate DA release in the striatum (Benloucif et al 1993;West and Galloway 1996;De Deurwaerdere et al 1997). Similarly, local application of 5-HT or 5-HT agonists have been shown to reduce (de Belleroche and Gardiner 1982) and facilitate dopamine efflux in the nucleus accumbens (Guan and McBride 1989;Parson and Justice 1993).…”

Section: The Modulating Effects Of Serotonin On Dopamine Neurotransmimentioning

confidence: 99%

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

Vollenweider

1999

Neuropsychopharmacology

255

138

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The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [ 11 C]raclopride to D 2 -dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n ϭ 7). Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HTPsilocybin, a potent indoleamine hallucinogen and 5-HT receptor stimulating agent, has been reported to produce a psychosis-like syndrome in man resembling the first manifestation of schizophrenia in certain respects [for review see (Fischman 1983;Gouzoulis-Mayfrank et al. 1998)]. Particularly, ego-disorders (Rüm-mele and Gnirss 1961;Vollenweider et al. 1997), affective changes (Rümmele and Gnirss 1961), loosened associations (Spitzer et al. 1996) and perceptual alterations commonly seen in psilocybin-induced psychosis are also observed in incipient acute schizophrenic stages (Bowers and Freedman 1966;Heimann, 1986;Gouzoulis et al. 1994). In support of these suggested clinical similarities, we recently found that psilocybin produced a marked prefrontal and anterior cingulate activation in normal subjects comparable to the hyperfrontal pattern observed in some (Cleghorn et al. 1989;Ebmeier et al. 1993Ebmeier et al. , 1995Catafau et al. 1994 1994;Ebmeier et al. 1995;Sabri et al. 1997) but not all (Andreasen et al. 1992;Buchsbaum et al. 1992;Liddle et al. 1992;Siegel et al. 1993) acute schizophrenic patients. A number of functional animal studies have suggested that indoleamine (psilocybin, LSD) and phenylethylamine (DOI, mescaline) hallucinogens produce their psychotomimetic effects primarily through excessive stimulation of 5-HT, and 5-HT 2A receptors in particular (McKenna et al. 1989;Pierce and Peroutka 1989;Aghajanian 1994;Sipes and Geyer 1994;Padich et al. 1996). This assumption was corroborated in a recent human study demonstrating that the psychotomimetic effects of psilocybin can be blocked dose-dependently by pretreatment with the preferential 5-HT 2A receptor antagonist ketanserin (Vollenweider et al. 1998). However, pretreatment with the D 2 -antagonist haloperidol also reduces some of the positive symptoms of psilocybin psychosis. This raises the possibility that symptoms of psilocybin are secondary responses to increased dopaminergic transmission (Vollenweider et al. 1998).Hence, a contribution of the dopamine systems to the effects of psilocybin, presumably through a serotonindopamine interaction, cannot be ruled out. Functional interactions between central serotonin (5-HT) and dopamine (DA) systems have been well documented. Electrophysiological, biochemical, and behavioral evidence suggests that the ascending serotonergic pathways from the medial and dorsal raphe modulate or control the function of the mesolimbic and mesostriatal dopamine systems (Joyce 1993;Zazpe et al. 1994;Kapur and Remington 1996). The modulating effect of serotonin on striatal dopamine release...

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Activation of a 5-HT3 receptor releases dopamine from rat striatal slice

Cited by 163 publications

References 4 publications

The properties of 5‐HT₃ receptors in clonal cell lines studied by patch‐clamp techniques

The properties of 5‐HT₃ receptors in clonal cell lines studied by patch‐clamp techniques

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

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Activation of a 5-HT3 receptor releases dopamine from rat striatal slice

Cited by 163 publications

References 4 publications

The properties of 5‐HT3 receptors in clonal cell lines studied by patch‐clamp techniques

The properties of 5‐HT3 receptors in clonal cell lines studied by patch‐clamp techniques

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

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The properties of 5‐HT₃ receptors in clonal cell lines studied by patch‐clamp techniques

The properties of 5‐HT₃ receptors in clonal cell lines studied by patch‐clamp techniques