Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia

Sumiyoshi, Tomiki; Stockmeier, Craig A.; Overholser, James C.; Dilley, Ginny E.; Meltzer, H.Y.

doi:10.1016/0924-977x(96)88299-x

Cited by 41 publications

(52 citation statements)

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“…Postmortem studies have reported that the density of 5-HT 1A receptors is increased in frontal and temporal cortices in schizophrenia (Burnet et al, 1996(Burnet et al, , 1997Gurevich and Joyce, 1997;Hashimoto et al, 1991;Simpson et al, 1996;Sumiyoshi et al, 1996). Positron emission tomography studies confirm an increase in cortical 5-HT 1A receptor binding in schizophrenia (Kasper et al, 2002;Tauscher et al, 2002).…”

Section: Discussionsupporting

confidence: 51%

Prevention of the Phencyclidine-Induced Impairment in Novel Object Recognition in Female Rats by Co-Administration of Lurasidone or Tandospirone, a 5-HT1A Partial Agonist

Horiguchi

Hannaway

Adelekun

et al. 2012

Neuropsychopharmacol

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Hypoglutamatergic function may contribute to cognitive impairment in schizophrenia (CIS). Subchronic treatment with the N-methyl-D-aspartate receptor antagonist, phencyclidine (PCP), induces enduring deficits in novel object recognition (NOR) in rodents. Acute treatment with atypical antipsychotic drugs (APDs), which are serotonin (5-HT) 2A /dopamine D 2 antagonists, but not typical APDs, eg, haloperidol, reverses the PCP-induced NOR deficit in rats. We have tested the ability of lurasidone, an atypical APD with potent 5-HT 1A partial agonist properties, tandospirone, a selective 5-HT 1A partial agonist, haloperidol, a D 2 antagonist, and pimavanserin, a 5-HT 2A inverse agonist, to prevent the development of the PCP-induced NOR deficit. Rats were administered lurasidone (0.1 or 1 mg/kg), tandospirone (5 mg/kg), pimavanserin (3 mg/kg), or haloperidol (1 mg/kg) b.i.d. 30 min before PCP (2 mg/kg, b.i.d.) for 7 days (day1-7), followed by a 7-day washout (day8-14). Subchronic treatment with PCP induced an enduring NOR deficit. Lurasidone (1 mg/kg) but not 0.1 mg/kg, which is effective to acutely reverse the deficit due to subchronic PCP, or tandospirone, but not pimavanserin or haloperidol, significantly prevented the PCP-induced NOR deficit on day 15. The ability of lurasidone co-treatment to prevent the PCP-induced NOR deficit was enduring and still present at day 22. The preventive effect of lurasidone was blocked by WAY100635, a selective 5-HT 1A antagonists, further evidence for the importance of 5-HT 1A receptor stimulation in the NOR deficit produced by subchronic PCP. Further study is needed to determine whether these results concerning mechanism and dosage can be the basis for prevention of the development of CIS in at risk populations.

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Section: Discussionsupporting

confidence: 51%

Prevention of the Phencyclidine-Induced Impairment in Novel Object Recognition in Female Rats by Co-Administration of Lurasidone or Tandospirone, a 5-HT1A Partial Agonist

Horiguchi

Hannaway

Adelekun

et al. 2012

Neuropsychopharmacol

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“…Also, the cognitive deficits of schizophrenia were found to be associated with abnormal neurotransmitter systems in the brain and with genetic mutations (Friston et al, 1991;Stefansson et al, 2009). Abnormal expression of neurotransmitter receptors occurs among schizophrenia in those brain regions that are related to cognitive deficits in verbal memory and attention (Crook et al, 2000;Newell et al, 2007;Sumiyoshi et al, 1996). For example, a reduction in M1 receptor protein in the hippocampus, superior temporal gyrus, and anterior cingulate cortex in schizophrenic subjects has been reported (Crook et al, 2000;Deng and Huang, 2005;Zavitsanou et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Gender differences in cognitive function of patients with chronic schizophrenia

Han¹,

Huang²,

Chen³

et al. 2012

Progress in Neuro-Psychopharmacology and Biological Psychiatry

120

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Schizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 122 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and antipsychotic dose (chlorpromazine equivalents). Almost all RBANS scores in the schizophrenics and healthy controls showed significant positive correlations with education. Thus, patients of both sexes with schizophrenia experienced more deteriorated performance than healthy controls on cognitive domains of immediate memory, language and delayed memory. Furthermore, male schizophrenic patients had more serious cognitive deficits than female patients in immediate and delayed memory, but not in language, visuospatial and attention indices. AbstractSchizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 172 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and antipsychotic dose (chlorpromazine equivalents). Almost all RBANS scores in the schizophrenics and healthy controls showed significant positive correlations with education. Thus, patients of both sexes with schizophrenia experienced more deteriorated performance than healthy controls on cognitive domains of immediate memory, language and delayed memory.Furthermore, male schizophrenic patients had more serious cognitive deficits than female patients in immediate and delayed memory, but not in language, visuospatial and attention indices.

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“…Among them, 5-HT 1A receptors are highly enriched in prefrontal cortex (Kia et al, 1996a;Feng et al, 2001). Increased prefrontal 5-HT 1A receptor density has been found in schizophrenia patients (Simpson et al, 1996;Sumiyoshi et al, 1996). Mice lacking 5-HT 1A receptors show elevated anxiety (Heisler et al, 1998;Ramboz et al, 1998), and this defect can be rescued by expression of 5-HT 1A receptors in the forebrain (Gross et al, 2002).…”

Section: Introductionmentioning

confidence: 92%

Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism

Yuen¹

2005

Journal of Neuroscience

207

197

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The serotonin system and NMDA receptors (NMDARs) in prefrontal cortex (PFC) are both critically involved in the regulation of cognition and emotion under normal and pathological conditions; however, the interactions between them are essentially unknown. Here we show that serotonin, by activating 5-HT 1A receptors, inhibited NMDA receptor-mediated ionic and synaptic currents in PFC pyramidal neurons, and the NR2B subunit-containing NMDA receptor is the primary target of 5-HT 1A receptors. This effect of 5-HT 1A receptors was blocked by agents that interfere with microtubule assembly, as well as by cellular knock-down of the kinesin motor protein KIF17 (kinesin superfamily member 17), which transports NR2B-containing vesicles along microtubule in neuronal dendrites. Inhibition of either CaMKII (calcium/calmodulin-dependent kinase II) or MEK/ERK (mitogen-activated protein kinase kinase/extracellular signalregulated kinase) abolished the 5-HT 1A modulation of NMDAR currents. Biochemical evidence also indicates that 5-HT 1A activation reduced microtubule stability, which was abolished by CaMKII or MEK inhibitors. Moreover, immunocytochemical studies show that 5-HT 1A activation decreased the number of surface NR2B subunits on dendrites, which was prevented by the microtubule stabilizer. Together, these results suggest that serotonin suppresses NMDAR function through a mechanism dependent on microtubule/kinesinbased dendritic transport of NMDA receptors that is regulated by CaMKII and ERK signaling pathways. The 5-HT 1A -NMDAR interaction provides a potential mechanism underlying the role of serotonin in controlling emotional and cognitive processes subserved by PFC.

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Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia

Cited by 41 publications

References 0 publications

Prevention of the Phencyclidine-Induced Impairment in Novel Object Recognition in Female Rats by Co-Administration of Lurasidone or Tandospirone, a 5-HT1A Partial Agonist

Prevention of the Phencyclidine-Induced Impairment in Novel Object Recognition in Female Rats by Co-Administration of Lurasidone or Tandospirone, a 5-HT1A Partial Agonist

Gender differences in cognitive function of patients with chronic schizophrenia

Serotonin 5-HT1A Receptors Regulate NMDA Receptor Channels through a Microtubule-Dependent Mechanism

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