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NEUROPHARMACOLOGY
Centre de Recherche Pierre Fabre, Castres Cedex, France
Received March 30, 2005; accepted June 23, 2005.
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Abstract |
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). Atypical antipsychotics, such as clozapine, olanzapine, and risperidone, antagonize D2-like receptors but also act by mechanisms involving other neurotransmitter systems. Thus, actions at serotonin receptors, with emphasis on 5-HT2A/2C receptor subtypes, have gained prominence as targets for antipsychotics (Ichikawa and Meltzer, 1999). Recently, converging preclinical and clinical evidence has increasingly drawn attention to the role of 5-HT1A receptors, suggesting that combining antagonist activity at dopamine D2 receptors with agonist activity at 5-HT1A receptors offers a promising strategy for the design of novel antipsychotics (see Meltzer et al., 2003).
5-HT1A receptors are up-regulated in frontal cortex of schizophrenics, as shown in postmortem autoradiography and positron emission tomography studies (Burnet et al., 1997; Tauscher et al., 2002), consistent with a role of 5-HT1A receptors in the pathophysiology of schizophrenia. Accordingly, antipsychotic drugs exhibiting 5-HT1A agonist properties are associated with several potential advantages. For example, 5-HT1A receptor activation lowers extrapyramidal symptom liability: in animal studies, 5-HT1A agonists reverse the cataleptic effects of conventional neuroleptics (e.g., Prinssen et al., 1999). Furthermore, 5-HT1A receptor agonists are active in models of anxiety and depression (Blier and Ward, 2003), suggesting enhanced treatment of negative symptoms. In addition, Sumiyoshi et al. (2001) have shown that adjunctive treatment with the 5-HT1A partial agonist, tandospirone, attenuates memory dysfunction in schizophrenia.
The neurochemical basis for beneficial properties of 5-HT1A receptor activation may be related to enhanced dopamine release in brain regions associated with cognitive function and consequent activation of D1 receptors controlling acetylcholine release therein (Consolo et al., 1996). In fact, activation of 5-HT1A receptors preferentially enhances dopamine release in the prefrontal cortex over that in the striatum or nucleus accumbens (Arborelius et al., 1993), and efficacy against negative symptoms in schizophrenia is associated with attenuation of functional impairment of mesocortical dopaminergic transmission (Weinberger and Berman, 1996). Accordingly, marked increases in frontocortical dopamine release are found with atypical antipsychotics such as clozapine, olanzapine, ziprasidone, and risperidone but not with conventional neuroleptics such as haloperidol (Volonte et al., 1997; Li et al., 1998; Rollema et al., 2000).
Among existing antipsychotics, clozapine, ziprasidone, and aripiprazole possess 5-HT1A agonist properties (Newman-Tancredi et al., 2005) but also act at numerous other targets (Shapiro et al., 2003). In contrast, a new generation of antipsychotics is gaining prominence, which selectively targets dopamine D2 receptors and 5-HT1A receptors without appreciable interactions at other sites. These drugs, now undergoing clinical development, include bifeprunox (Wolf, 2003), SSR181507 (Claustre et al., 2003; Depoortere et al., 2003), and SLV313 (Glennon et al., 2002) as well as the antidyskinetic agent, sarizotan (Bartoszyk et al., 2004). However, only sparse information is available concerning the pharmacological properties of these drugs, and the relative influence of their 5-HT1A agonist properties on the modulation of serotonergic and dopaminergic transmission remains unclear.
Therefore, we examined, in uniform experimental conditions, the effect of these drugs on two neurochemical measures. First, the 5-HT1A agonist properties of the drugs were examined by measuring the decrease in extracellular 5-HT in rat hippocampus, a region that has been widely used to assess activation of somatodendritic 5-HT1A receptors in the raphe (e.g., Assié and Koek, 2000). Specific mediation of this response by 5-HT1A receptors was demonstrated by antagonism with the selective 5-HT1A antagonist WAY100635. Second, the influence of antipsychotics on dopaminergic neurotransmission was examined by measuring dopamine levels in medial prefrontal cortex. 5-HT1A receptor control of dopamine release in frontal cortex is complex and may involve both pre- and postsynaptic 5-HT1A receptors via GABAergic and glutamatergic systems (Celada et al., 2001). By comparing the actions of the antipsychotics on these two neurochemical parameters, we demonstrate that 5-HT1A receptor activation plays widely differing roles in the actions of antipsychotics and suggest that novel drugs selectively targeted at D2 and 5-HT1A receptors may display distinctive profiles.
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Materials and Methods |
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Microdialysis Procedure. Rats were anesthetized with chloral hydrate (400-500 mg/kg i.p.). A guide cannula with a dummy probe was stereotaxically implanted into the medial prefrontal cortex, stereotaxic coordinates: rostral, +3.0 mm; lateral, +0.8 mm; ventral, -1.7 mm, from bregma or the hippocampus; stereotaxic coordinates, rostral -4.8 mm; lateral, +4.6 mm; and ventral, -4.6 mm, from bregma and skull surface. Two additional holes were drilled for skull screws, and the guide was secured with dental cement.
Following surgery and recovery from anesthesia, animals were return to their home cage. At the end of the day, each rat was placed in a microdialysis cage. On the following day, the dummy probe was replaced by a microdialysis probe (3-mm length, 0.5-mm diameter; CMA/Microdialysis, Solna, Sweden). The probe was continuously perfused (1.1 µl/min) with artificial cerebrospinal fluid (140 mM NaCl, 3 mM KCl, 2.5 mM CaCl2, 1 mM MgCl2, 1.2 mM Na2HPO4, 0.27 mM NaH2PO4, and 7.2 mM glucose). When measuring 5-HT in the hippocampus, basal levels amounted to approximately 5 fmol/sample, and decreases in 5-HT could not be reliably determined. For this reason, citalopram was included in the perfusion medium, thus increasing basal 5-HT levels. Following a 2-h stabilization period, samples were collected every 20 min. After four baseline samples, saline or WAY100635 was injected s.c., followed 40 min later by administration of the antipsychotics, and samples were collected for 140 min after administration of the latter drug.
At the end of the experiment, the animal was killed by injection of a lethal dose of pentobarbital (160 mg/kg i.p.), and the brain was removed, frozen, and cut in a cryomicrotome (Jung Frigocut 2800; Reichart-Jung, NuBlock, Germany) to verify the placement of the probe.
Analytical Procedure. Analysis of dopamine or 5-HT was performed by means of an online high-pressure liquid chromatography system with electrochemical detection equipped with a reversephase column (Lichrocart 125-2, Superspher 100 RP-18, 119-mm length, 2-mm internal diameter, 4-µm granulometry; Merck, Darmstadt, Germany). The mobile phase: 0.15 M NaH2PO4, 0.1 mM EDTA, 0.1 mM 1-octanesulfonic acid sodium salt, and 14% methanol, pH 5.2, for the measure of dopamine and 0.15 M NaH2PO4, 0.1 mM EDTA, 0.7 mM 1-octanesulfonic acid sodium salt, and 15% methanol, pH 4.6, for the measure of 5-HT) was pumped through the column at a rate of 0.2 ml/min (HPLC-118 solvent module; Beckman Coulter, Fullerton CA). Dopamine or 5-HT eluted from the column (retention time 5-6 and 7-9 min, respectively) was measured with a glassy carbon working electrode maintained at a potential of +0.64 V versus Ag/AgCl reference electrode (DECADE detector; ANTEC Leyden BV, Leiden, The Netherlands). Data were acquired using a Beckman 32 Karats system. Concentrations of dopamine or 5-HT were estimated by comparing peak areas from the microdialysis samples with those of external standards of known concentration of the compounds. The limit of detection (3 times baseline noise) was approximately 1 fmol/20 µl sample.
Data Analysis. Data were analyzed using repeated measures analysis of variance carried out with the mixed procedure of SAS version 8.2 software (SAS Institute, Cary, NC). Mean AUC values for the 140-min period after administration of the compounds were analyzed by one-way ANOVA followed by Dunnett's test where appropriate (SigmaStat; SPSS Inc., Chicago, IL). For each compound, the ED50 value was determined by linear interpolation between the two doses that increase dopamine levels or decrease 5-HT levels with amounts bordering 50% (vehicle control as 0% and maximal effect of each compound as 100%).
Drugs. (+)8-OH-DPAT hydrobromide, haloperidol, risperidone, and clozapine were purchased from Sigma/RBI (Natick, MA), and chloral hydrate was purchased from Acros (Geel, Belgium). Pentobarbital sodium was purchased from Ceva Santé Animale (Libourne, France). Citalopram hydrobromide and SLV313 were kindly donated by Lundbeck (Copenhagen, Denmark) and Solvay-Duphar (Weesp, The Netherlands), respectively. Olanzapine, ziprasidone hydrochloride, nemonapride, aripiprazole, bifeprunox (DU127090 [GenBank] ) mesylate, sarizotan (EMD-128130) hydrochloride, SSR181507, and WAY100635 were synthesized at the Centre de Recherche Pierre Fabre. The doses of compounds were expressed as the base. WAY100635, SSR181507, and (+)8-OH-DPAT were dissolved in distilled water; haloperidol, clozapine, olanzapine, risperidone, and SLV313 were dissolved in distilled water with a drop of lactic acid, after which the pH was adjusted to 5 to 7 with 1 N sodium hydroxide; all other compounds were suspended in distilled water by adding Tween 80 (2 drops/10 ml); the injection volume was 10 ml/kg.
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Results |
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Haloperidol (0.16-2.5 mg/kg), nemonapride (0.63-10 mg/kg), aripiprazole (2.5-40 mg/kg), and bifeprunox (0.63-10 mg/kg) did not significantly alter extracellular dopamine (Figs. 1 and 2). Clozapine (2.5-40 mg/kg), olanzapine (0.63-40 mg/kg), risperidone (0.16-10 mg/kg), ziprasidone (0.16-10 mg/kg), sarizotan (0.63-40 mg/kg), SLV313 (0.04-0.63 mg/kg), and SSR181507 (2.5-40 mg/kg), like the 5-HT1A agonist (+)8-OH-DPAT (0.16-2.5 mg/kg), produced a dose-dependent increase in extracellular dopamine concentration (ED50 values; Table 2). The effects of sarizotan (2.5 mg/kg), SLV313 (0.16 mg/kg), and SSR181507 (10 mg/kg), like those of (+)8-OH-DPAT (0.63 mg/kg), were reversed by the selective 5-HT1A antagonist, WAY100635 (0.16 mg/kg). In contrast, the effects of clozapine, olanzapine, risperidone, and ziprazidone were not significantly antagonized by WAY100635.
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Extracellular Concentrations of Serotonin in the Ventral Hippocampus. The mean basal extracellular concentration of 5-HT in the rat ventral hippocampus was 38.9 ± 0.9 fmol/20 µl (n = 227).
Haloperidol (2.5 mg/kg), risperidone (2.5 mg/kg), clozapine (2.5-40 mg/kg), olanzapine (40 mg/kg), ziprasidone (2.5-40 mg/kg), and aripiprazole (2.5-40 mg/kg) produced no significant change in extracellular concentrations of 5-HT (Figs. 3 and 4). Nemonapride (0.63-10 mg/kg), bifeprunox (0.63-40 mg/kg), sarizotan (0.63-10 mg/kg), SLV313 (0.16-2.5 mg/kg), and SSR181507 (0.63-10 mg/kg), like (+)8-OH-DPAT (0.16-2.5 mg/kg), induced a dose-dependent, significant decrease in extracellular 5-HT levels (ED50 values; Table 2). These effects were antagonized by WAY100635.
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For a summary of the statistical analyses of data, see Table 1.
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Discussion |
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Increases in medial prefrontal cortex dopamine levels are associated with attenuated cognitive dysfunction and negative symptoms in schizophrenia (Meltzer and McGurk, 1999). Correspondingly, several atypical antipsychotics, including clozapine, olanzapine, risperidone, and ziprasidone, preferentially increase dopamine release in the prefrontal cortex (Volonte et al., 1997; Li et al., 1998; Rollema et al., 2000). Because 5-HT1A agonists preferentially increase dopamine release in this brain area (Arborelius et al., 1993; Ichikawa et al., 2001), the 5-HT1A agonist properties of certain antipsychotics may play a role in these effects. However, the contribution of 5-HT1A receptor activation to the actions of different antipsychotics is heterogeneous. Clozapine and ziprasidone, multireceptor agents that act as partial agonists at 5-HT1A receptors in vitro, may increase dopamine release in frontal cortex partly by actions at 5-HT1A sites (Rollema et al., 2000) although their actions at these targets are, at best, modest. In contrast, risperidone and olanzapine have little or no interaction at 5-HT1A receptors and enhance frontocortical dopamine release by indirect 5-HT1A receptor activation (Ichikawa et al., 2001). In comparison, recent drugs that selectively target both D2-like and 5-HT1A receptors, such as SLV313, SSR181507, and bifeprunox, would be expected to display accentuated serotonergic actions at 5-HT1A receptors (Newman-Tancredi et al., 2005). The present study investigated the role of 5-HT1A receptor activation in the neurochemical profile of conventional and new generation antipsychotics under uniform experimental conditions and thus constitutes a powerful homogenous database to compare the various compounds.
Influence of Antipsychotics on Serotonin Release in Hippocampus. 5-HT levels in the hippocampus were determined as a measure of somatodendritic 5-HT1A receptor activation. Indeed, 5-HT1A receptors located in the raphe nuclei exert inhibitory control of serotonergic neurotransmission and, consequently, reduce 5-HT release in terminal regions (Blier and Ward, 2003). Even drugs with low efficacy at 5-HT1A receptors, such as the partial agonist buspirone (e.g., Assié and Koek, 2000), are capable of inhibiting 5-HT release as a result of the high 5-HT1A autoreceptor reserve in the raphe (Cox et al., 1993). Here, the new putative antipsychotics, SSR181507, SLV313, and bifeprunox, like nemonapride, the antidyskinetic agent, sarizotan, and the protopypical 5-HT1A agonist (+)8-OH-DPAT, decrease extracellular 5-HT in the hippocampus (Figs. 1 and 2), actions that were reversed by 5-HT1A receptor blockade. These observations are consistent with the marked in vitro 5-HT1A agonist properties of these compounds (Newman-Tancredi et al., 2005). In contrast, aripiprazole, which exhibits only weak agonist properties at 5-HT1A receptors in vitro, showed little capacity to inhibit serotonin release, whereas olanzapine, risperidone, and haloperidol did not influence serotonin release, consistent with their absence of interaction with 5-HT1A receptors.
Influence of Antipsychotics on Dopamine Release in Medial Prefrontal Cortex. The present data on influence of established antipsychotics on medial prefrontal cortex dopamine release are generally similar to those reported in individual studies by other laboratories. Thus, the increase in dopamine release by ziprasidone is consistent with data from Rollema et al. (2000), although its effects here were not reversed by WAY100635 pretreatment. In contrast, the increase in dopamine release induced by risperidone tended to be attenuated by WAY100635, in agreement with a previous report (Ichikawa et al., 2001). In view of the low affinity of risperidone for 5-HT1A receptors, an indirect mechanism involving the 5-HT2A antagonist properties of the compound has been proposed (Ichikawa et al., 2001). Indeed, 5-HT1A and 5-HT2A receptors are colocalized in the frontal cortex (Amargós-Bosch et al., 2004), and cross talk between these receptors occurs at the signal transduction and electrophysiological level (Ashby et al., 1994). The effects of clozapine (14-fold increase of dopamine at 40 mg/kg) and olanzapine (8-fold increase of dopamine at 40 mg/kg) are considerably more pronounced than those of the other compounds studied here (maximal increase 2.5-fold). In a previous study, the effects of clozapine were attenuated by 5-HT1A receptor blockade (Rollema et al., 1997), but under present conditions and in agreement with other laboratories (Millan et al., 1998), the effects of clozapine and olanzapine were not reversed by WAY100635, reflecting their weak interaction at 5-HT1A receptors. In fact, clozapine and olanzapine interact at multiple receptor subtypes, and their induction of dopamine release is related to antagonism of 5-HT2A/2C receptors (Ichikawa et al., 2001) and 
2 adrenoceptors (Devoto et al., 2003). Furthermore, activation of muscarinic receptors by clozapine and its principal metabolite, desmethyl-clozapine, also contributes to release of dopamine (Li et al., 2004b).
The putative antipsychotics, SSR181507, SLV313, and bifeprunox, selectively target dopamine D2-like and 5-HT1A receptors (Newman-Tancredi et al., 2005), with little interaction with a range of other receptors including 5-HT2 or adrenergic receptors (Claustre et al., 2003; Wolf, 2003; M. B. Assié, unpublished data). Therefore, they represent a new generation of antipsychotic agents, and the present study provides the first comparative data of these drugs on 5-HT and dopamine release. In agreement with Claustre et al. (2003), SSR181507 increased dopamine levels in a dose-dependent manner and in a similar dose range as for inhibition of serotonin release in hippocampus (Table 2). In contrast, SLV313 potently increased dopamine release at doses 8-fold lower than those that inhibit serotonin release (Table 2), whereas sarizotan and (+)8-OH-DPAT exerted their influence on dopamine and serotonin release at similar doses. All these responses in both hippocampus and medial prefrontal cortex were abolished by pretreatment with WAY100635, indicating mediation by 5-HT1A receptors. It may be speculated that the ligands differentially influence neurotransmitter release in different brain structures according to their balance of affinity/efficacy at 5-HT1A receptors and dopaminergic sites.
In contrast to these drugs, aripiprazole and bifeprunox did not increase dopamine release, consistent with their reported partial agonist properties at D2 receptors and their only moderate efficacy and affinity, respectively, for 5-HT1A receptors (Wolf, 2003; Newman-Tancredi et al., 2005). The absence of effects of aripiprazole on dopamine release confirms previous observations (Jordan et al., 2004), although a recent report indicates that it slightly increased dopamine release at a low dose of 0.3 mg/kg (Li et al., 2004a). Under present conditions, aripiprazole failed to increase dopamine release even at this low dose (0.31 mg/kg i.p.; AUC value, 85 ± 10%). In comparison, although nemonapride has high efficacy at 5-HT1A receptors (Assié et al., 1997), it did not increase dopamine release, likely because of its potent dopamine D2 antagonist properties. Indeed, in measures of catalepsy in rats, nemonapride exhibits 5-HT1A properties at doses 60-fold greater than those that antagonize D2 receptors (Prinssen et al., 1998).
Summary and Conclusions. In summary, the present study provides a comparison of the influence of 5-HT1A receptor activation on the release of serotonin and dopamine by established and novel antipsychotic agents. Different groups of compounds may be defined. First, compounds such as clozapine, olanzapine, risperidone, and ziprasidone have weak or negligible actions at 5-HT1A receptors, as assessed by their absence of influence on serotonin release. These drugs nevertheless influence dopamine release in medial prefrontal cortex (Fig. 4) but do so predominantly via other receptor mechanisms, such as blockade of 5-HT2A receptors. Second, aripiprazole and bifeprunox exert little influence on dopamine release, a consequence of their partial agonist properties at D2 receptors. Third, SSR181507, SLV313, and sarizotan exhibit pronounced serotonergic properties, inhibiting 5-HT release in hippocampus in a manner similar to the 5-HT1A agonist (+)8-OH-DPAT. These drugs, which interact with D2-like receptors but are devoid of marked interactions at other receptor subtypes, increase cortical dopamine release by direct 5-HT1A receptor activation. This distinctive profile of action on serotonin and dopamine release may translate into an innovative pattern of therapeutic properties. However, additional investigation would be desirable, in particular by extending these studies to other brain regions, such as nucleus accumbens and striatum. Furthermore, no information is currently available concerning regulation of somatodendritic 5-HT1A autoreceptor function following chronic administration of these drugs. Electrophysiological studies demonstrated desensitization of raphe cells after chronic administration of 5-HT1A receptor agonists (Blier and Ward, 2003). In accordance, microdialysis studies have shown that the ability of a challenge dose of 5-HT1A agonist to decrease terminal 5-HT release was altered after chronic administration of 5-HT1A receptor agonists (Kreiss and Lucki, 1997; Casanovas et al., 1999). In addition, Hensler and Durgham (2001), using [35S]GTP
S autoradiography, have shown that the regulation of presynaptic 5-HT1A receptor function following repeated administration of 8-OH-DPAT involves changes in receptor-G protein interaction. Thus, the regulation of 5-HT and dopamine release following chronic administration of existing and novel antipsychotics may reveal additional complexity (Hernandez and Hoebel, 1995).
In conclusion, considerable diversity exists in the contribution that 5-HT1A receptor activation makes to the neurochemical profile of antipsychotic agents. A new generation of drugs is in clinical development that selectively targets dopamine D2-like and 5-HT1A receptors, and although additional investigation is required to fully elucidate their actions, these compounds may display distinctive properties in the treatment of mood deficits, negative symptoms, and cognitive dysfunction in schizophrenic patients.
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Acknowledgements |
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Footnotes |
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). Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
ABBREVIATIONS: 5-HT, 5-hydroxytryptamine; SSR181507, (3-exo)-8-benzoyl-N-(((2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl)methyl)-8-azabicyclo(3.2.1)octane-3-methanamine; SLV313, 1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-4-[5-(4-fluorophenyl)-pyridin-3-ylmethyl]-piperazine; WAY100635, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide; AUC, area under the curve; ANOVA, analysis of variance; (+)8-OH-DPAT, (+)-8-hydroxy-2-(di-n-propylamino)tetralin.
Address correspondence to: Marie-Bernadette Assié, Centre de Recherche Pierre Fabre, 17 Avenue Jean Moulin, 81106 Castres Cedex, France. E-mail: marie.bernadette.assie{at}pierre-fabre.com
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References |
|---|
|
TopAbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Amargós-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, Toth M, Mengod G, and Artigas F (2004) Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Cereb Cortex 14: 281-299.
Arborelius L, Nomikos GG, Hacksell U, and Svensson TH (1993) (R)-8-OH-DPAT preferentially increases dopamine release in rat medial prefrontal cortex. Acta Physiol Scand 148: 465-466.[Medline]
Ashby CR, Edwards E, and Wang RY (1994) Electrophysiological evidence for a functional interaction between 5-HT1A and 5-HT2A receptors in the rat medial prefrontal cortex: an iontophoretic study. Synapse 17: 173-181.[CrossRef][Medline]
Assié M-B, Cosi C, and Koek W (1997) 5-HT1A receptor agonist properties of the antipsychotic, nemonapride: comparison with bromerguride and clozapine. Eur J Pharmacol 334: 141-147.[CrossRef][Medline]
Assié M-B and Koek W (2000) Estimation of apparent pA2 values for WAY 100635 at 5-HT1A receptors regulating 5-hydroxytryptamine release in anaesthetised rats. Eur J Pharmacol 409: 173-177.[CrossRef][Medline]
Assié M-B, Ravailhe V, Faucillon V, and Newman-Tancredi A (2004) Effects of antipsychotics with diverse dopamine D2 and serotonin 5-HT1A properties on cerebral dopamine and serotonin levels in rats. Int J Neuropsychopharmacol 7: P02.506.
Bartoszyk GD, Van Amsterdam C, Greiner HE, Rautenberg W, Russ H, and Seyfried CA (2004) Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand: I. Neurochemical profile. J Neural Transm 111: 113-126.
Blier P and Ward NM (2003) Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry 53: 193-203.[CrossRef][Medline]
Burnet PW, Eastwood SL, and Harrison PJ (1997) [3H]WAY-100635 for 5-HT1A receptor autoradiography in human brain: a comparison with [3H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia. Neurochem Int 30: 565-574.[CrossRef][Medline]
Casanovas JM, Vilaró MT, Mengod G, and Artigas F (1999) Differential regulation of somatodendritic serotonin 5-HT1A receptors by 2-week treatments with the selective agonists alnespirone (S-20499) and 8-hydroxy-2-(di-n-propylamino)tetralin: microdialysis and autoradiographic studies in rat brain. J Neurochem 72: 262-272.[Medline]
Celada P, Puig MV, Casanovas JM, Guillazo G, and Artigas F (2001) Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: involvement of serotonin-1A, GABAA and glutamate receptors. J Neurosci 21: 9917-9929.
Claustre Y, De Peretti D, Brun P, Gueudet C, Allouard N, Alonso R, Lourdelet J, Oblin A, Damoiseau G, Françon D, et al. (2003) SSR181507, a dopamine D2 receptor antagonist and 5-HT1A receptor agonist: I. Neurochemical and electrophysiological profile. Neuropsychopharmacology 28: 2064-2076.[Medline]
Consolo S, Ramponi S, Ladinsky H, and Baldi G (1996) A critical role for D1 receptors in the 5-HT1A-mediated facilitation of in vivo acetylcholine release in rat frontal cortex. Brain Res 707: 320-323.[CrossRef][Medline]
Cox RF, Meller E, and Waszczak BL (1993) Electrophysiological evidence for a large receptor reserve for inhibition of dorsal raphe neuronal firing by 5-HT1A agonists. Synapse 14: 297-304.[CrossRef][Medline]
Depoortere R, Boulay D, Perrault G, Bergis O, Decobert M, Françon D, Jung M, Simiand J, Soubrié P, and Scatton B (2003) SSR181507, a dopamine D2 receptor antagonist and 5-HT1A receptor agonist: II. Behavioral profile predictive of an atypical antipsychotic activity. Neuropsychopharmacology 28: 1889-1902.[Medline]
Devoto P, Flore G, Vacca G, Pira L, Arca A, Casu MA, Pani L, and Gessa GL (2003) Co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex induced by clozapine, the prototype atypical antipsychotic. Psychopharmacology 167: 79-84.[Medline]
Glennon J, McCreary AC, Ronken E, Siarey R, Hesselink MB, Feenstra R, Van Vliet B, Long SK, and Kruse CG (2002) SLV313 is a dopamine D2 receptor antagonist and serotonin 5-HT1A agonist: in vitro and in vivo neuropharmacology. Eur Neuropsychopharmacol 12: S277.
Harvey PD and Bowie CR (2003) Cognitive deficits in schizophrenia: early course and treatment. Clin Neurosci Res 3: 17-22.
Hensler JG and Durgham H (2001) Regulation of 5-HT1A receptor-stimulated [35S]-GTPS binding as measured by quantitative autoradiography following chronic agonist administration. Br J Pharmacol 132: 605-611.[CrossRef][Medline]
Hernandez L and Hoebel BG (1995) Chronic clozapine selectively decreases prefrontal cortex dopamine as shown by simultaneous cortical, accumbens and striatal microdialysis in freely moving rats. Pharmacol Biochem Behav 52: 581-589.[CrossRef][Medline]
Ichikawa J, Ishii H, Bonaccorso S, Fowler WL, O'Laughlin IA, and Meltzer HY (2001) 5-HT2A and D2 receptor blockade increases cortical DA release via 5-HT1A receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem 76: 1521-1531.[CrossRef][Medline]
Ichikawa J and Meltzer HY (1999) Relationship between dopaminergic and serotonergic neuronal activity in the frontal cortex and the action of typical and atypical antipsychotic drugs. Eur Arch Psychiat Clin Neuros 249: 90-98.
Jordan S, Koprivica V, Dunn R, Tottori K, Kikuchi T, and Altar CA (2004) In vivo effects of aripiprazole on cortical and striatal dopaminergic and serotonergic function. Eur J Pharmacol 483: 45-53.[CrossRef][Medline]
Kreiss DS and Lucki I (1997) Chronic administration of the 5-HT1A receptor agonist 8-OH-DPAT differentially desensitizes 5-HT1A autoreceptors of the dorsal and median raphe nuclei. Synapse 25: 107-116.[CrossRef][Medline]
Li XM, Perry KW, Wong DT, and Bymaster FP (1998) Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum. Psychopharmacology 136: 153-161.[CrossRef][Medline]
Li Z, Ichikawa J, Dai J, and Meltzer HY (2004a) Aripiprazole, a novel antipsychotic drug, preferentially increases dopamine release in the prefrontal cortex and hippocampus in rat brain. Eur J Pharmacol 493: 75-83.[CrossRef][Medline]
Li Z, Ichikawa J, Huang M, Dai J, and Meltzer HY (2004b) N-desmethylclozapine (NDMC), an active metabolite of clozapine (CLO), increases cortical dopamine (DA) and acetylcholine (ACH) release via stimulation of M1 muscarinic receptors. Soc Neurosci Abstr 350: 15.
Meltzer HY, Li Z, Kaneda Y, and Ichikawa J (2003) Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharm Biol Psychiatry 27: 1159-1172.[CrossRef][Medline]
Meltzer HY and McGurk SR (1999) The effects of clozapine, risperidone and olanzapine on cognitive function in schizophrenia. Schizophr Bull 25: 233-255.
Millan MJ, Gobert A, Newman-Tancredi A, Audinot V, Lejeune F, Rivet JM, Cussac D, Nicolas JP, Muller O, and Lavielle G (1998) S 16924 ((R)-2-{1-[2-(2,3-dihydrobenzo[1,4]dioxin-5-yloxy)-ethyl]-pyrrolidin-3yl}-1-(4-fluoro-phenyl)-ethanone), a novel potential antipsychotic with marked serotonin (5-HT)1A agonist properties: I. Receptorial and neurochemical profile comparison with clozapine and haloperidol. J Pharmacol Exp Ther 286: 1341-1355.
Newman-Tancredi A, Assié M-B, Leduc N, Ormière A-M, Danty N, and Cosi C (2005) Novel antipsychotics activate recombinant human and native rat serotonin 5-HT1A receptors: affinity, efficacy and potential implication for treatment of schizophrenia. Int J Neuropsychopharmacol 11: 1-16.
Prinssen EP, Kleven MS, and Koek W (1998) The cataleptogenic effects of the neuroleptic nemonapride are attenuated by its 5-HT1A receptor agonist properties. Eur J Pharmacol 356: 189-192.[Medline]
Prinssen EPM, Kleven MS, and Koek W (1999) Interactions between neuroleptics and 5-HT1A ligands in preclinical behavioral models for antipsychotic and extrapyramidal effects. Psychopharmacology 144: 20-29.[CrossRef][Medline]
Rollema H, Lu Y, Schmidt AW, Sprouse JS, and Zorn SH (2000) 5-HT1A receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex. Biol Psychiatry 48: 229-237.[CrossRef][Medline]
Rollema H, Lu Y, Schmidt AW, and Zorn SH (1997) Clozapine increases dopamine release in prefrontal cortex by 5-H1A receptor activation. Eur J Pharmacol 338: R3-R5.[CrossRef][Medline]
Shapiro DA, Renock S, Arrington E, Chiodo LA, Liu LX, Sibley DR, Roth BL, and Mailman R (2003) Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 28: 1400-1411.[CrossRef][Medline]
Sumiyoshi T, Matsui M, Yamashita I, Nohara S, Kurachi M, Uehara T, Sumiyoshi S, Sumiyoshi C, and Meltzer HY (2001) The effect of tandospirone, a serotonin1A agonist, on memory function in schizophrenia. Biol Psychiatry 49: 861-868.[CrossRef][Medline]
Tauscher J, Kapur S, Verhoeff NPLG, Hussey DF, Daskalakis ZJ, Tauscher-Wisniewski S, Wilson AA, Houle S, Kasper S, and Zipursky RB (2002) Brain serotonin 5-HT1A receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635. Arch Gen Psychiatry 59: 514-520.
Volonte M, Monferini E, Cerutti M, Fodritto F, and Borsini F (1997) BIMG 80, a novel potential antipsychotic drug: evidence for multireceptor actions and preferential release of dopamine in prefrontal cortex. J Neurochem 69: 182-190.[Medline]
Weinberger DR and Berman KF (1996) Prefrontal function in schizophrenia: confounds and controversies. Philos Trans R Soc Lond B Biol Sci 351: 1495-1503.[Medline]
Wolf W (2003) DU-127090. Curr Opin Investig Drugs 4: 72-76.[Medline]
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