Detection of TOAD-64 in adult rat brain as revealed by two-dimensional protein gel electrophoresis followed by MALDI mass spectrometry possible modulatory effect of chronic haloperidol treatment

The molecular mechanisms by which antipsychotic effects are achieved remain largely elusive. Possible mechanisms include the modulation of nerve cell gene expression. The antipsychotic drug haloperidol was administered orally (1.6 mg/kg) to adult rats for 3 weeks. Protein patterns in striata and forebrains were studied by two-dimensional gel electrophoresis (2-DE). One differentially regulated protein spot was identified by matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) after trypsin digest. Turned on after devision-64 kD (TOAD-64), the identified protein, was present in all gels and, in addition, was up-regulated in the striata but not in the forebrains of the haloperidol-treated animals by 43%. It is concluded that TOAD-64, typically regarded as a marker for commitment to neuronal differentiation during fetal development, also plays a role in adult rat forebrain and striatum and that its concentration is possibly modulated by haloperidol treatment.