Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics

Mita, Tatsuo; Hanada, Susumu; Nishino, Norikazu; Kuno, Toshiki; Nakai, Hisao; Yamadori, Takashi; Mizoi, Y; Tanaka, Chikako

doi:10.1016/0006-3223(86)90332-x

Cited by 226 publications

(96 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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...

show abstract

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

View full text Add to dashboard Cite

show abstract

“…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: 98%

“…The density of 5-HT2 receptors, la beled with [3H]lysergic acid diethylamide ([3H]LSD) or [3H]ketanserin, has been shown to be reduced (Ben nett et al 1979;Mita et al 1986), unchanged, or in creased (Whitaker et al 1981;Reynolds et al 1983) in the frontal cortex of schizophrenic cases. Again, vari ability in results may be caused by the inclusion of in dividuals whose death occurred by suicide, as there have been reports of increased densities of 5-HT recep tors (Stanley and Mann 1983;Mann et al 1986;Arango et al 1990;Arora and Meltzer 1989a) and decreased den sities (Crow et al 1984;Gross-Isseroff et al 1990) for suicide cases.…”

mentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…To examine possible co-regulation of RGS2 and the serotonin 2A receptor (5-HT2AR), the density of the 5-HT2AR of the BA9 of control subjects was also examined by measuring 3 H-Ketanserin binding (Mita et al, 1986). The experiment was performed according to the one described previously (Ono et al, 2002).…”

Section: Western Blot Analysis and 3 H-ketanserin Binding Assaymentioning

confidence: 99%

Association of RGS2 Gene Polymorphisms with Suicide and Increased RGS2 Immunoreactivity in the Postmortem Brain of Suicide Victims

Cui

Nishiguchi

Ivleva

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Regulators of G-protein signaling are a family of proteins that negatively regulate the intracellular signaling of G protein-coupled receptors, such as the serotonin receptor. Recent studies have suggested that one of these proteins, the regulator of G-protein signaling 2 (RGS2), plays an important part in anxiety and/or aggressive behavior. To explore the involvement of the RGS2 gene in the vulnerability to suicide, we screened Japanese suicide victims for sequence variations in the RGS2 gene and carried out an association study of RGS2 gene polymorphisms with suicide victims. In the eight identified polymorphisms that were identified by mutation screening, we genotyped four common single-nucleotide polymorphisms (SNPs) in the RGS2 gene, and found significant differences in the distribution of the SNP3 (C + 2971G, rs4606) genotypes and alleles of the SNP2 (C-395G, rs2746072) and the SNP3 between completed suicides and the controls. The distribution of the haplotype was also significantly different between the two groups (global po0.0001). Furthermore, RGS2 immunoreactivity significantly increased in the amygdala and the prefrontal cortex (Brodmann area 9 (BA9)) of the postmortem brain of the suicide subjects. These findings suggest that RGS2 is genetically involved in the biological susceptibility to suicide in the Japanese population.

show abstract

Decreased serotonin S2 and increased dopamine D2 receptors in chronic schizophrenics

Cited by 226 publications

References 16 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

Association of RGS2 Gene Polymorphisms with Suicide and Increased RGS2 Immunoreactivity in the Postmortem Brain of Suicide Victims

Contact Info

Product

Resources

About