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A systematic microdialysis study of dopamine transmission in the accumbens shell/core and prefrontal cortex after acute antipsychotics

Abstract

Rationale

The only systematic in vivo studies comparing antipsychotic (AP) effects on nucleus accumbens (NAc) shell and core dopamine (DA) transmission are voltammetric studies performed in pargyline-pretreated, halothane-anaesthetized rats. Studies in freely moving rats not pretreated with pargyline are not available. This study was intended to fill this gap by the use of in vivo microdialysis in freely moving rats.

Methods

Male Sprague-Dawley rats were implanted with microdialysis probes in the NAc shell and core and medial prefrontal cortex (PFCX). The next day, rats were administered intravenously with two or three doses of APs, and dialysate DA was monitored in 10-min samples. Some rats were pretreated with pargyline (75 mg/kg i.p.) and after 1 h were given clozapine or risperidone.

Results

Clozapine, risperidone, quetiapine, raclopride, sulpiride and amisulpride increased DA preferentially in the NAc shell. Such preferential effect on shell DA was not observed after haloperidol, chlorpromazine and olanzapine. In contrast to voltammetric studies, a preferential effect on NAc core DA was not observed after any dose of AP. Pargyline pretreatment did not reduce but actually amplified the preferential effect of clozapine and risperidone on NAc shell DA.

Conclusions

Apart from raclopride and olanzapine, the APs with lower extrapyramidal effects could be distinguished from typical APs on the basis of their ability to preferentially stimulate DA transmission in the NAc shell. There was no relationship between stimulation of PFCX DA and atypical APs profile. The differences between this study and voltammetry studies were not attributable to pargyline pretreatment.

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Acknowledgments

This study was supported by the National Research Council of Italy (CNR), by the Ministero dell’Università e della Ricerca (MURST/MIUR) and by the Regione Autonoma della Sardegna (RAS).

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Authors do not have any conflict of interest to declare.

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Correspondence to Gaetano Di Chiara.

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Gianluigi Tanda and Valentina Valentini contributed equally to this work.

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Tanda, G., Valentini, V., De Luca, M.A. et al. A systematic microdialysis study of dopamine transmission in the accumbens shell/core and prefrontal cortex after acute antipsychotics. Psychopharmacology 232, 1427–1440 (2015). https://doi.org/10.1007/s00213-014-3780-2

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Keywords

  • Dopamine
  • Microdialysis
  • Accumbens shell
  • Accumbens core
  • Prefrontal cortex
  • Second-generation antipsychotics