Dopamine and serotonin interactions in the prefrontal cortex: Insights on antipsychotic drugs and their mechanism of action

被引：62

作者：

Di Pietro, N. C. ^{[1
]}

Seamans, J. K. ^{[1
]}

机构：

[1] Univ British Columbia, Dept Psychiat, Brain Res Ctr, UBC Hosp, Vancouver, BC V6T 2R5, Canada

来源：

PHARMACOPSYCHIATRY | 2007年 / 40卷

关键词：

V PYRAMIDAL CELLS; EXCITATORY POSTSYNAPTIC CURRENTS; NMDA RECEPTOR HYPOFUNCTION; FAST-SPIKING INTERNEURONS; ATYPICAL ANTIPSYCHOTICS; NUCLEUS-ACCUMBENS; 5-HT1A RECEPTORS; IN-VIVO; SYNAPTIC ACTIVITY; PIRIFORM CORTEX;

D O I：

10.1055/s-2007-992133

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Diminished activity within the prefrontal cortex (PFC) has been associated with many of the cognitive deficits that are observed in schizophrenia. It has been hypothesized that antipsychotic drugs (APDs) used to treat schizophrenia restore normal activity by antagonizing the dopamine (DA) D2 receptor, which is also known to modulate key ionic currents in the PFC. However, the hypothesis that an under-active cortical DA system is responsible for schizophrenic symptoms has been challenged by evidence that newer atypical APDs are weak antagonists at the D2 receptor but potent antagonists at the serotonin (5-HT) 2A receptor [57]. This review examines how DA and 5-HT modulate cortical activity and how they may interact in ways that are relevant to schizophrenia. It is concluded that although D2 receptor antagonism remains a critical factor in restoring impaired cortical activity, effects on 5-HT receptors may act in a synergistic manner on NMDA and GABA currents to potentiate antipsychotic actions in the PFC.

引用

页码：S27 / S33

页数：7

共 103 条

[1] Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release [J].

Aghajanian, GK ;

Marek, GJ .

BRAIN RESEARCH, 1999, 825 (1-2) :161-171

[2] Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells [J].

Aghajanian, GK ;

Marek, GJ .

NEUROPHARMACOLOGY, 1997, 36 (4-5) :589-599

[3] 5-HYDROXYTRYPTAMINE2 AND 5-HYDROXYTRYPTAMINE1A RECEPTORS MEDIATE OPPOSING RESPONSES ON MEMBRANE EXCITABILITY IN RAT-ASSOCIATION CORTEX [J].

ARANEDA, R ;

ANDRADE, R .

NEUROSCIENCE, 1991, 40 (02) :399-412

[4] A pre- and postsynaptic modulatory action of 5-HT and the 5-HT2A, 2C receptor agonist DOB on NMDA-evoked responses in the rat medial prefrontal cortex [J].

Arvanov, VL ;

Liang, XF ;

Magro, P ;

Roberts, R ;

Wang, RY .

EUROPEAN JOURNAL OF NEUROSCIENCE, 1999, 11 (08) :2917-2934

[5] Contrasting contribution of 5-hydroxytryptamine 1A receptor activation to neurochemical profile of novel antipsychotics:: Frontocortical dopamine and hippocampal serotonin release in rat brain [J].

Assié, MB ;

Ravailhe, V ;

Faucillon, V ;

Newman-Tancredi, A .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 315 (01) :265-272

[6] Role of serotonin2A receptors in the D-amphetamine-induced release of dopamine:: comparison with previous data on α1b-adrenergic receptors [J].

Auclair, A ;

Blanc, G ;

Glowinski, J ;

Tassin, JP .

JOURNAL OF NEUROCHEMISTRY, 2004, 91 (02) :318-326

[7] Serotonergic facilitation of synaptic activity in the developing rat prefrontal cortex [J].

Béïque, JC ;

Chapin-Penick, EM ;

Mladenovic, L ;

Andrade, R .

JOURNAL OF PHYSIOLOGY-LONDON, 2004, 556 (03) :739-754

[8] Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex [J].

Beique, Jean-Claude ;

Imad, Mays ;

Mladenovic, Ljiljana ;

Gingrich, Jay A. ;

Andrade, Rodrigo .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (23) :9870-9875

[9] The activation of 5-HT2A receptors in prefrontal cortex enhances dopaminergic activity [J].

Bortolozzi, A ;

Díaz-Mataix, L ;

Scorza, MC ;

Celada, P ;

Artigas, F .

JOURNAL OF NEUROCHEMISTRY, 2005, 95 (06) :1597-1607

[10] The effects of clozapine and haloperidol on serotonin-1A, -2A and -2C receptor gene expression and serotonin metabolism in the rat forebrain [J].

Burnet, PWJ ;

Chen, CPLH ;

McGowan, S ;

Franklin, M ;

Harrison, PJ .

NEUROSCIENCE, 1996, 73 (02) :531-540

← 1 2 3 4 5 6 7 8 9 10 →