Antipsychotic and antidepressant co-treatment: effects on transcripts of inducible postsynaptic density genes possibly implicated in behavioural disorders.
Selective serotonin reuptake inhibitors (SSRIs) and antipsychotics co-administration is a widely used strategy to treat both psychotic depression and depressive symptoms in schizophrenia. Nonetheless, the molecular mechanisms involved in the therapeutic benefits of antidepressant-antipsychotic combination are still elusive. It has been suggested that co-administration of SSRIs and antipsychotics may result in molecular changes different from their individual effects. In the present study, we evaluated the acute effects of two SSRIs, citalopram and escitalopram, alone or in combination with haloperidol, on the expression of Homer1a together with its splice variant ania-3, and p11, two genes linked respectively to dopaminergic and serotonergic neurotransmission and involved in synaptic plasticity. Homer1a and ania-3 were induced in the striatum by haloperidol, alone and in combination with SSRIs, but not by SSRIs only. Haloperidol+citalopram co-administration induced a stronger Homer1a expression than haloperidol alone in the ventrolateral caudate-putamen. No signal was detected for p11 in striatum, while there were no significant differences among treatments in cortical subregions. Homer1a was significantly down-regulated in the parietal cortex by all treatments. These results demonstrated that haloperidol+citalopram combination exerts synergistic effects on Homer expression, suggesting that citalopram may influence the impact by haloperidol on the dopaminergic neurotransmission. Moreover, present findings confirm that Homer1a and ania-3 are strongly induced in striatum by haloperidol, while they are not influenced by citalopram or escitalopram in this region. Oppositely, in the cortex the two transcripts are modulated by both haloperidol and SSRIs, suggesting a possible role of both dopamine and serotonin in their cortical regulation.
Dell'aversano
Carmela
C
Laboratory of Molecular Psychiatry and Pharmacotherapeutics, Department of Neuroscience, Section of Psychiatry, University School of Medicine "Federico II", Edificio 18, Via Sergio Pansini 5, 80131 Naples, Italy.
Tomasetti
Carmine
C
Iasevoli
Felice
F
de Bartolomeis
Andrea
A
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage*; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D015283:Citalopram / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D015870:Gene Expression / Q000187:drug effects*; D006220:Haloperidol / Q000008:administration & dosage; D000072233:Homer Scaffolding Proteins; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D009435:Synaptic Transmission / Q000235:genetics
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D002352:Carrier Proteins; D015283:Citalopram; D006220:Haloperidol; D000072233:Homer Scaffolding Proteins; D012333:RNA, Messenger; D017367:Selective Serotonin Reuptake Inhibitors