Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients

Arora, Ramesh; Meltzer, Herbert Y.

doi:10.1007/bf01244654

Cited by 152 publications

(62 citation statements)

References 39 publications

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“…Nevertheless, the present findings suggest that stimulation of 5-HT, presumably 5-HT 2 and 5-HT 1 receptors, can lead to an increase in striatal dopamine efflux which may contribute to the psychotomimetic effects of psilocybin. Of particular interest to the present study are indications that abnormalities in the number of 5-HT 1A and 5-HT 2A receptors have been found in the frontal cortex, nucleus accumbens, striatum, and hippocampi of schizophrenic patients (Mita et al 1986;Arora and Meltzer 1991;Joyce et al 1993;Laruelle et al 1993;Gurevich and Joyce 1997). Thus, the present data also support further evaluation of the 5-HT system in the pathophysiology of schizophrenia (Meltzer 1991).…”

Section: Discussionsupporting

confidence: 75%

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

Vollenweider

1999

Neuropsychopharmacology

261

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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Section: Discussionsupporting

confidence: 75%

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

Vollenweider

1999

Neuropsychopharmacology

261

138

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“…4 (middle laminae), temporal cortex (middle laminae), and hippocampus but not altered in the frontal, anteri or cingulate, or motor cortices. Previous studies (Arora and Meltzer 1991 ;Mita et al 1986) reported fmding a de crease in [3H]spiroperidol or [3H]ketanserin binding to 5-HT2 receptors in the frontal cortex of schizophreni cs as compared to controls. They attributed the results to a reduction in the maximum number of 5-HT2 sites and not to a change in the affinity of the compounds for the 5-HT2 sites.…”

Section: Alterations In Schizophreniamentioning

confidence: 99%

Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics

Joyce

Shane

Lexow

et al. 1993

Neuropsychopharmacol

329

142

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Serotonin (5-HT) uptake sites were mapped by autoradiographic means with PH]cyano-imipramine , the 5-HTIA receptor with [3HJ8-hydroxy-2-[di-n-propyl-amino]tetralin ([3HJ8-0H-DPAT), and the 5-HTz receptor with both pH]ketanserin and {l251]1ysergic acid diethylamide ([lZ5IJLSD) in eight nonneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomallmatrix campartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern � either 5-HTz or 5-HTIA receptors. For the isocortex, a general organizational scheme was observed with the 5-HTIA receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the cambined distributions of the 5-HTIA receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was camplementary to the distribution of 5-HTIA and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomallmatrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HTIA receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HTIA receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotoninz receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n "" 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific.

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“…How ever, the results are controversial. Increased (Whitaker et al 1981), decreased (Bennett et al 1979;Mita et al 1986;Arora and Meltzer 1991;Laruelle et al 1991) or normal (Mackay et al 1978;Owen et al 1981;Reynolds et al 1983) 5-HT2 binding has been reported in the frontal cortex of neuroleptic-treated schizophrenic pa tients. Because neuroleptic drugs may downregulate 5-HT2 receptors in rodent brain (Andree et al 1986;Lee and Tang 1984), these results could be influenced by neuroleptic treatment.…”

mentioning

confidence: 99%

Effect of Clozapine Treatment on Serotonin-2—Receptor Binding in the Blood Platelets of Schizophrenic Patients

Arora

Meltzer

1994

Neuropsychopharmacol

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Serotonin2 (5-HT2) receptor binding in the frontal cortex of schizophrenic patients

Cited by 152 publications

References 39 publications

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

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

Serotonin Uptake Sites and Serotonin Receptors Are Altered in the Limbic System of Schizophrenics

Effect of Clozapine Treatment on Serotonin-2—Receptor Binding in the Blood Platelets of Schizophrenic Patients

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