AUTORADIOGRAPHIC LOCALIZATION OF CCK-8 BINDING-SITES IN THE RAT-BRAIN - EFFECTS OF CHRONIC METHAMPHETAMINE ADMINISTRATION ON THESE SITES

The effects of chronic methamphetamine (MAP) administration (at a dose of 4 mg/kg for 14 days) on [H-3]pCCK-8 binding sites in the rat brain were investigated by an in vitro quantitative receptor autoradiographic technique. The number of [H-3]pCCK-8 binding sites was significantly reduced in layers III and IV of the medial frontal, anterior, and posterior cingulate cortices, in layers II-IV of the retrosplenial cortex, in layers III-VI of the dorsal insular cortex, and in the reticular nucleus of the thalamus, compared to these numbers in a control group of rats that received physiologic saline. Further, chronic methamphetamine administration led to a significant increase in the number of these binding sites in layer I of the entorhinal cortex. These findings indicate the CCK peptides in the limbic lobe may be closely related to the development of the behavioral changes associated with methamphetamine sensitization. In addition, these results provide supporting evidence for the involvement of the limbic system in the pathophysiology of schizophrenia.