Differential effects of topiramate on prefrontal glutamatergic transmission when combined with raclopride or clozapine.

Treatment with topiramate may improve negative symptoms in schizophrenia when added to typical antipsychotic drugs (APDs) but not to clozapine. Both dopaminergic and glutamatergic transmissions in the medial prefrontal cortex (mPFC) are facilitated by atypical, but not typical, APDs, which is thought to improve negative symptoms and cognitive dysfunction in schizophrenia. Our previous results show that topiramate increases prefrontal dopamine (DA) outflow when added to the D(2/3) receptorantagonist raclopride.

Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia.

Rationale: Asenapine is a novel psychopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder.

Materials And Methods: The present study was undertaken to investigate the effects of asenapine using animal models predictive of antipsychotic efficacy (conditioned avoidance response [CAR]) and extrapyramidal side effects (EPS; catalepsy). In parallel, the effects of asenapine on regional dopamine output using in vivo microdialysis in freely moving rats, dopamine output in the core and shell subregions of nucleus accumbens (NAc) using in vivo voltammetry in anesthetized rats, and N-methyl-D: -aspartate (NMDA)-induced currents in pyramidal neurons of the medial prefrontal cortex (mPFC) using the electrophysiological technique intracellular recording in vitro were assessed.

Inhibition of the glycine transporter GlyT-1 potentiates the effect of risperidone, but not clozapine, on glutamatergic transmission in the rat medial prefrontal cortex.

Clinical studies suggest that the efficacy of the atypical antipsychotic drug (APD) risperidone (but not clozapine) can be augmented by adjunctive treatment with agonists at the glycine site of the N-methyl-D-aspartate (NMDA) receptor. By using intracellular recording, we have investigated the effect of the glycine transporter-1 (GlyT-1) inhibitor N [3-(4'-fluorophenyl)-3-(4'phenylphenylphenoxy) propyl] sarcosine (NFPS) on NMDA-induced currents in pyramidal cells of the medial prefrontal cortex (mPFC), both when given alone and in combination with either risperidone or clozapine. Both risperidone and clozapine enhanced the NMDA-induced currents.

The combination of nicotine with the D2 antagonist raclopride or the weak D4 antagonist L-745,870 generates a clozapine-like facilitation of NMDA receptor-mediated neurotransmission in pyramidal cells of the rat medial prefrontal cortex.

Clozapine and other atypical, but not typical, antipsychotic drugs (APDs), facilitate both dopaminergic and N-methyl-D-aspartate (NMDA) receptor-mediated glutamatergic transmission in the medial prefrontal cortex (mPFC), which is thought to improve cognition. Switching schizophrenic patients from typical APDs to clozapine may reduce their cigarette smoking. Here, we tested whether nicotine, which facilitates dopamine release, also facilitates NMDA receptor-mediated neurotransmission in the mPFC, when given alone or in combination with a D(2,3) antagonist, raclopride, or a D4 antagonist, 3-(4-[4-chlorophenyl]piperazin-1-yl)methyl-1H-pyrrolo[2,3b]pyridine (L-745,870), using intracellular recording in pyramidal cells of the rat mPFC.