Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum

Westerink, Ben H.C.; Kawahara, Yukie; Boer, P. A. J. De; Geels, C.; Vries, J. B. De; Wikström, Håkan; Kalkeren, Annette A. van; Vliet, B. Van; Kruse, Chris G.; Long, Sihui

doi:10.1016/s0014-2999(00)00935-3

Cited by 107 publications

(56 citation statements)

References 28 publications

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“…In contrast to studies employing the administration of 5-HT2A antagonists alone, the combined, systemic administration of D2 and 5-HT2A receptor antagonists results in a potentiation of DA release (Westerink et al, 2001;Liegeois et al, 2002). Although the exact mechanism is not clear, evidence has been provided that this effect may be mediated by a combined potent 5-HT2A and relatively weak D2 receptor effect interacting with 5-HT1A receptor-regulated brain mechanisms (Bonaccorso et al, 2002;Ichikawa et al, 2001).…”

Section: Discussionmentioning

confidence: 96%

“…Indeed, this combination of properties may explain why the systemic administration of higher doses (1 mg/kg) of risperidone produces increases in mPFC DA efflux (Hertel et al, 1996;Kuroki et al, 1999;Zhang et al, 2000). Lower doses of risperidone (0.004 mg/ kg), like M100907, do not alter cortical DA efflux (Westerink et al, 1998(Westerink et al, , 2001). These lower doses may result in more selective effects on 5-HT2A receptors and are closer to the range employed clinically.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

Pehek

Nocjar

Roth

et al. 2005

Neuropsychopharmacol

174

104

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The mechanism(s) by which serotonin modulates dopamine release in the medial prefrontal cortex is not known, although studies suggest an involvement of 5-HT2 family receptors. We employed in vivo microdialysis and putatively selective 5-HT2A antagonists (M100907, MDL 11,939, SR46349B) to determine if 5-HT2A receptors are responsible for both drug-and stress-induced DA release in the medial prefrontal cortex. MDL 11,939 and SR46349B receptor-binding studies indicated, for the first time, that only MDL 11,939 had greater selectivity for the 5-HT2A vs the 5-HT2C receptor subtypes similar to M100907, and that both showed low or no affinity for non-5-HT2 receptors. Reverse dialysis with 5-HT2A antagonists had little or no effect on basal dopamine efflux. However, intracortical administration of MDL 11,939 or M100907 attenuated dopamine release induced by systemic administration of the 5-HT2 agonist DOI. Dual-probe microdialysis demonstrated that systemic DOI also increased glutamate concentrations in the ventral tegmental area (VTA). This was blocked by intracortical M100907. Cortical perfusion with M100907, or the atypical antipsychotic drug risperidone, but not the 5-HT2B/C ligand SB 206553, also decreased dopamine release induced physiologically by stress. These results indicate that stimulation of cortical 5-HT2A receptors increases the release of dopamine from the mesocortical system. They suggest that this effect may be mediated by increases in glutamate release from corticotegmental projections to the VTA. Additionally, they indicate that cortical 5-HT2A receptors modulate evoked dopamine release, such as that observed physiologically following mild stress. These findings may have implications for the pharmacological treatment of disorders resulting from or exacerbated by stress.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

Pehek

Nocjar

Roth

et al. 2005

Neuropsychopharmacol

174

104

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“…clusion of nomifensine, a DA uptake inhibitor, in the perfusion medium that elevates basal DA levels potentiated the D 2/3 receptor antagonist raclopride-induced DA release in the mPFC (Westerink et al 2001), suggesting the relatively weak ability of D 2 receptors to tonically inhibit DA release in that region (Ozaki et al 1989), compared with that in the NAC or STR. We also considered that potential damage of cholinergic neurons by probe implantation, as suggested by a gradual decrease in basal ACh release, could have contributed to the lack of an effect of scopolamine on ACh release in the STR or NAC.…”

Section: Discussionmentioning

confidence: 98%

Atypical, but Not Typical, Antipsychotic Drugs Increase Cortical Acetylcholine Release without an Effect in the Nucleus Accumbens or Striatum

Ichikawa

2002

Neuropsychopharmacology

229

124

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The role of acetylcholine (ACh) in the action of antipsychotic drugs (APDs) was studied by microdialysis, without AChesterase inhibition, to facilitate the interpretation of any observed drug effects. The atypical APDs, (Perry et al. 1999) and working memory (Winkler et al. 1995), and thus, may be important to either the cognitive dysfunction of schizophrenia or the ability of antipsychotic drugs (APDs) to improve some or all aspects of that cognitive deficit (Meltzer and McGurk 1999). The atypical APDs, clozapine, olanzapine, risperidone, and quetiapine, have, in fact, been reported to improve some domains of cognitive dysfunction (see Meltzer and McGurk 1999; Purdon 1999 for reviews), in addition to psychopathology (Leucht et al. 1999) in schizophrenia, more so than typical APDs, e.g., haloperidol and phenothiazines. The basis for these advantages is unclear.The atypical APDs share in common a relatively more potent antagonist action at serotonin (5-HT) 2A NO . 3 al. 1989;Schotte et al. 1996) and ␣ 1 -and ␣ 2 -adrenoceptors (Hertel et al. 1999). These features have been related to their ability to increase DA release in the mPFC (Hertel et al. 1999; Kuroki et al. 1999; Ichikawa et al. 2001). However, a possible role for ACh in mediating these effects is receiving increasing attention. Clozapine and olanzapine, but not risperidone, quetiapine, ziprasidone, or iloperidone (Schotte et al. 1996;Bymaster et al. 1999), have significant direct agonist or antagonist effects upon various subtypes of muscarinic ACh receptors (mAChRs) (Tandon 1999), whereas the typical APDs, thioridazine and mesoridazine, are also potent mAChR antagonists (Niedzwiecki et al. 1989a,b;Bolden et al. 1992). Furthermore, trihexyphenidyl and biperiden (Bolden et al. 1992), mAChR antagonists which reduce typical APD-induced extrapyramidal symptoms (EPS), have been reported to cause complex clinical effects in patients with schizophrenia, e.g., working memory impairment (King 1990) and worsening of psychosis while decreasing negative symptoms (Tandon et al. 1992). It is possible that clozapine and olanzapine influence clinical symptoms in schizophrenia via a direct effect upon main cholinergic transmission (Zorn et al. 1994; Bymaster et al. 1996).As has been demonstrated in rodents (Everitt and Robbins 1997) and primates (Mrzljak et al. 1995), the nucleus basalis magnocellularis (NBM) or the basal forebrain consisting of the substantia innominata, the nucleus of Meynert, and the horizontal limb of the diagonal band, project cholinergic neurons to the cortex, whereas cholinergic interneurons exist mostly in the striatum (STR) and nucleus accumbens (NAC) (Kawaguchi et al. 1995). These three regions are involved in various actions of APDs (Ichikawa and Meltzer 1999): 1) the medial prefrontal cortex (mPFC) has been suggested to be involved in the neural circuitry important for negative symptoms and cognition, e.g., working memory (Goldman-Rakic and Selemon 1997); 2) the STR is centrally involved in motor function; and 3) the NAC plays a key ...

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“…In contrast to studies employing the administration of 5-HT2A receptor antagonists alone, the combined, systemic administration of D2 and 5-HT2A receptor antagonists results in a potentiation of cortical DA release (Westerink et al, 2001;Liegeois et al, 2002). Evidence has been provided that this effect may be mediated by actions of released 5-HT interacting with 5-HT1A receptors (Bonaccorso et al, 2002).…”

Section: Mesocortical Pathwaymentioning

confidence: 95%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

535

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum

Cited by 107 publications

References 28 publications

Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

Evidence for the Preferential Involvement of 5-HT2A Serotonin Receptors in Stress- and Drug-Induced Dopamine Release in the Rat Medial Prefrontal Cortex

Atypical, but Not Typical, Antipsychotic Drugs Increase Cortical Acetylcholine Release without an Effect in the Nucleus Accumbens or Striatum

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

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