| Unraveling monoamine receptors involved in the action of typical and atypical antipsychotics on glutamatergic and serotonergic transmission in prefrontal cortex. | | Unraveling monoamine receptors involved in the action of typical and atypical antipsychotics on glutamatergic and serotonergic transmission in prefrontal cortex. | López-Gil X., Artigas F. and Adell A. (2010) Curr. Pharm. Des. 16: 502-515. | 2009-12-31T23:00:00Z | <div style="text-align:justify;"></div><h3 style="line-height:1.2857;margin:0px;font-weight:bold;display:inline;text-align:justify;"><span class="ms-rteThemeForeColor-2-5 ms-rteThemeFontFace-1 ms-rteFontSize-2">Abstract</span></h3><div><h3 style="line-height:1.2857;margin:0px;color:#985735;font-weight:bold;display:inline;text-align:justify;"><br class="ms-rteThemeFontFace-1 ms-rteFontSize-2"></h3><div style="color:#000000;text-align:justify;"><p style="margin-bottom:0.5em;"><span class="ms-rteThemeFontFace-1 ms-rteFontSize-2">The systemic administration of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists has been considered as a pharmacological model of schizophrenia. In the present work, we used in vivo microdialysis to examine: first, the effects of MK-801, on the efflux of glutamate and serotonin (5-HT) in the medial prefrontal cortex (mPFC) of the rat; second, whether the MK-801-induced changes in the cortical efflux of both transmitters could be blocked by atypical (clozapine and olanzapine) and classical (haloperidol and chlorpromazine) antipsychotic drugs given intra-mPFC; and third, the role of local blockade of dopamine D(2)/D(3)/D(4), serotonin 5-HT(2A) and alpha(1)-adrenergic receptors as well as agonism at dopamine D(1)/D(5) and 5-HT(1A) receptors in the mPFC on the increased efflux of glutamate and 5-HT elicited by MK-801. The four antipsychotic drugs blocked the MK-801-induced increase in glutamate, whereas only clozapine and olanzapine were able to block the increased efflux of 5-HT. Furthermore, M100907 (5-HT(2A) antagonist), BAY x 3702 (5-HT(1A) agonist) and prazosin (alpha(1)-adrenergic antagonist) blocked the MK-801-induced increase of 5-HT and glutamate in the mPFC. In contrast, raclopride (D(2)/D(3) antagonist) and L-745,870 (D(4) antagonist) were able to prevent the increased efflux of glutamate (but not that of 5-HT) elicited by MK-801. SKF-38393 (dopamine D(1)/D(5) agonist) also prevented the MK-801-induced increase of glutamate in the mPFC, but the same effect on cortical 5-HT was reached only at the highest concentration tested. We suggest that the blockade of an exacerbated 5-HT release in the mPFC induced by NMDA antagonists can be a characteristic of atypical antipsychotic drugs. Moreover, we propose that D(2)/D(3)/D(4) receptor antagonists would act predominantly on a subpopulation of GABAergic interneurons of the mPFC, thus enhancing cortical inhibition, which would prevent an excessive glutamatergic transmission. Dopamine D(1)/D(5) agonists would further stimulate GABA release from other subpopulation of interneurons controlling cortical output to the dorsal raphe nucleus. Atypical antipsychotic drugs might further act upon 5-HT(2A), 5-HT(1A) and alpha(1)-adrenoceptors present in pyramidal cells (including those projecting to the dorsal raphe nucleus), which would directly inhibit an excessive excitability of these cells.<br></span></p></div></div> | <p><span class="ms-rteFontSize-3" style="margin:0px;padding:0px;border:0px;font-stretch:inherit;line-height:inherit;font-family:"yanone kaffeesatz";vertical-align:baseline;color:#474f51;text-align:justify;background-color:#ffffff;">[</span><a href="http://www.ncbi.nlm.nih.gov/pubmed/19909228" style="color:#ed391b;margin:0px;padding:0px;border:0px;font-stretch:inherit;font-size:18px;line-height:1.6;font-family:"yanone kaffeesatz";vertical-align:baseline;text-align:justify;background-color:#ffffff;"><span class="ms-rteFontSize-3" style="margin:0px;padding:0px;border:0px;font-style:inherit;font-stretch:inherit;line-height:inherit;font-family:inherit;vertical-align:baseline;">PubMed</span></a><span class="ms-rteFontSize-3" style="margin:0px;padding:0px;border:0px;font-stretch:inherit;line-height:inherit;font-family:"yanone kaffeesatz";vertical-align:baseline;color:#474f51;text-align:justify;background-color:#ffffff;">]</span><br></p> | 18 | | |
