Effect of Methamphetamine and Dopamine Receptor Antagonists on Cholecystokininlike Immunoreactivity in the Rat Medial Prefrontal Cortex

Abstract

A single intraperitoneal administration of methamphetamine (MAP) reduces cholecystokininlike immunoreactivity (CCK-LI) in medial prefrontal cortex (mPFC) of the rat brain. This report examines the effects of various dopamine (DA) receptor antagonists [haloperidol (HAL), sulpiride (SUL), YM09151-2 (YM), and SCH23390 (SCH)] on MAP-induced abnormal behaviors and the changes of CCK-LI in the rat mPFC. A single subcutaneous administration of HAL (0.25 mg/kg), YM (0.1 mg/kg), or SUL (250 mg/kg) significantly reduced the basal CCK-LI in mPFC by 20–40%; a selective D 1 antagonist, SCH (up to 1.0 mg/kg), had no effect on basal CCK-LI. However, the reduction of CCK-LI induced by MAP (20–40%) was abolished by the pretreatment with HAL (0.025 and 0.25 mg/kg), YM (0.01 and 0.1 mg/kg), or SCH (1.0 mg/kg), without being affected by SUL (up to 250 mg/kg). This effect of DA antagonists on MAP-induced change in CCK-LI was associated with an inhibition of MAP-induced stereotyped behaviors. These data suggest that the CCK-containing neurons in rat mPFC are functionally related to the mesocortical DA system and may participate in a development of abnormal behaviors induced by MAP.