Cholecystokinin binding sites in the rat forebrain: effects of acute and chronic methamphetamine administration

Using the in vitro quantitative receptor autoradiographical technique, changes in the binding parameters of [propionyl-3H] propionylated CCK-8 [( 3H]pCCK-8) binding sites in the rat forebrain were investigated following acute and chronic administration of methamphetamine (MAP). The (Kd)app values of [3H]pCCK-8 binding sites in the frontal medial cortex and anterior cingulate cortex were significantly reduced after a single injection of 4mg/kg MAP. On the other hand, chronic treatment (14 days) with MAP at this dose significantly decreased the Bmax value of [3H]pCCK-8 binding sites in the anterior cingulate cortex accompanied by supersensitivity of locomotor effects to MAP. These findings suggest that dopamine (DA) neurons in these two regions are functionally related to intrinsic CCK-containing cortical neurons, and that CCK subsensitivity, perhaps due to an alteration in DA transmission, is involved in MAP sensitization. These findings may be relevant to the DA hypothesis of schizophrenia.