6533b829fe1ef96bd1289b52

RESEARCH PRODUCT

Phencyclidine-induced disruption of oscillatory activity in prefrontal cortex: Effects of antipsychotic drugs and receptor ligands

Laia Lladó-pelfortLaia Lladó-pelfortEva Troyano-rodriguezEva Troyano-rodriguezAna Cervera-ferriH.e. Van Den MunkhofH.e. Van Den MunkhofPau CeladaPau CeladaM. Núñez-calvetM. Núñez-calvetFrancesc ArtigasFrancesc ArtigasN. JuradoN. Jurado

subject

Male0301 basic medicineOscillationsmedicine.drug_classDopamine AgentsAtypical antipsychoticPhencyclidineKainate receptorPharmacologyNeurotransmissionPrefrontal cortex03 medical and health scienceschemistry.chemical_compoundSerotonin Agents0302 clinical medicineHistamine AgentsmedicineAnimalsPharmacology (medical)NMDA receptor antagonistsAntipsychotic drugsRats WistarChlorpromazineEvoked PotentialsPhencyclidineBiological PsychiatryPharmacologyRacloprideAnalysis of VarianceDose-Response Relationship DrugFourier AnalysisChemistryElectroencephalographyPsychotomimeticRatsPsychiatry and Mental health030104 developmental biologyNeurologynervous systemSchizophreniaNBQXNeurology (clinical)Excitatory Amino Acid AntagonistsNeuroscience030217 neurology & neurosurgeryAntipsychotic Agentsmedicine.drug

description

The non-competitive NMDA receptor (NMDA-R) antagonist phencyclidine (PCP) markedly disrupts thalamocortical activity, increasing excitatory neuron discharge and reducing low frequency oscillations (LFO, <4Hz) that temporarily group neuronal discharge. These actions are mainly driven by PCP interaction with NMDA-R in GABAergic neurons of the thalamic reticular nucleus and likely underlie PCP psychotomimetic activity. Here we report that classical (haloperidol, chlorpromazine, perphenazine) and atypical (clozapine, olanzapine, quetiapine, risperidone, ziprasidone, aripripazole) antipsychotic drugs - but not the antidepressant citalopram - countered PCP-evoked fall of LFO in the medial prefrontal cortex (mPFC) of anesthetized rats. PCP reduces LFO by breaking the physiological balance between excitatory and inhibitory transmission. Next, we examined the role of different neurotransmitter receptors to reverse PCP actions. D2-R and D1-R blockade may account for classical antipsychotic action since raclopride and SCH-23390 partially reversed PCP effects. Atypical antipsychotic reversal may additionally involve 5-HT1A-R activation (but not 5-HT2A-R blockade) since 8-OH-DPAT and BAYx3702 (but not M100907) fully countered PCP effects. Blockade of histamine H1-R (pyrilamine) and ¿1-adrenoceptors (prazosin) was without effect. However, the enhancement of GABAA-R-mediated neurotransmission (using muscimol, diazepam or valproate) and the reduction of excitatory neurotransmission (using the mGluR2/3 agonist LY379268 and the preferential kainite/AMPA antagonist CNQX - but not the preferential AMPA/kainate antagonist NBQX) partially or totally countered PCP effects. Overall, these results shed new light on the neurobiological mechanisms used by antipsychotic drugs to reverse NMDA-R antagonist actions and suggest that agents restoring the physiological excitatory/inhibitory balance altered by PCP may be new targets in antipsychotic drug development.

yearjournalcountryeditionlanguage
2016-03-01
10.1016/j.euroneuro.2015.11.015http://hdl.handle.net/10261/148766