Methamphetamine-sensitized rats show augmented dopamine release to methylphenidate stimulation: A positron emission tomography using [18F]fallypride

Abstract

Previous studies demonstrated that patients with schizophrenia show greater sensitivity to psychostimulants than healthy subjects. Sensitization to psychostimulants and resultant alteration of dopaminergic neurotransmission in rodents have been suggested as a useful model of schizophrenia. This study was aimed to examine the use of methylphenidate as a psychostimulant to induce dopamine release and that of [18F]fallypride as a radioligand to estimate the release in a rat model of schizophrenia. Six rats were scanned by positron emission tomography (PET) twice before and after methylphenidate challenge to evaluate dopamine release. After the scans, these rats were sensitized by using repeated methamphetamine (MAP) administration. Then, they were re-scanned twice again before and after methylphenidate challenge to evaluate whether MAP-sensitized rats show greater sensitivity to methylphenidate. We revealed a main effect of MAP-pretreatment and that of metylphenidate challenge. We found that % change of distribution volume ratio after repeated administration of MAP was greater than that before sensitization. These results suggest that methylphenidate-induced striatal dopamine release increased after sensitization to MAP. PET scan using [18F]fallypride at methylphenidate-challenge may provide a biological marker for schizophrenia and be useful to diagnose schizophrenia.