EFFECTS OF INTRACRANIAL INFUSIONS OF CHLORDIAZEPOXIDE ON SPATIAL-LEARNING IN THE MORRIS WATER MAZE .1. NEUROANATOMICAL SPECIFICITY

The present investigation sought to determine the neuroanatomical locu s through which the amnesic and anxiolytic effects of the benzodiazepi ne agonist chlordiazepoxide are mediated. Rats were infused with eithe r chlordiazepoxide (60 nmol/mu l) or artificial CSF (1 mu l) into eith er the frontal cortex, nucleus basalis magnocellularis/substantia inno minata, amygdala, medial septum, hippocampus, or cerebellum and run in the open held to assess anxiety as thigmotaxia and in the Morris mate r maze to assess spatial learning. Other rats were given chlordiazepox ide (5 mg/kg) or saline (1 ml/kg) systemically and run in the open fie ld and water maze. When chlordiazepoxide was administered systemically , rats showed significantly less thigmotaxia, but not overall activity , than controls in the open held, and were deficit in spatial learning , but not cue learning or swim speed, in the water maze. Intracranial infusions revealed a neuroanatomical specificity for the amnesic and a nxiolytic actions of chlordiazepoxide. Infusions of chlordiazepoxide i nto the amygdala, but none of the other structures, reduced thigmotaxi a without affecting overall activity levels whereas infusions into the medial septum, but none of the other structures, prevented spatial le arning, but not cue learning, and reduced swim speed in the water maze . Together, these finding suggest that the medial septum and the amygd ala mediate the amnesic and anxiolytic actions of chlordiazepoxide, re spectively. Moreover, these results provide direct evidence that the a mnesic and anxiolytic actions of chlordiazepoxide are independent.