Investigating the cognitive effects of atypical antipsychotics: The Noradrenergic hypothesis

Abstract

<P>IMPROVEMENT IN COGNITIVE FUNCTIONING (E.G. WORKING MEMORY) HAS BECOME ONE OF THE MOST IMPORTANT CLINICAL TARGETS IN THE TREATMENT OF SCHIZOPHRENIA. ATYPICAL ANTIPSYCHOTIC DRUGS ARE SUPERIOR FOR COGNITIVE IMPAIRMENTS IN SCHIZOPHRENIA THAN THE TYPICAL DRUGS.YET THE MECHANISM OF THE IMPROVEMENT REMAINS ELUSIVE. ATYPICAL ANTIPSYCHOTIC MEDICATIONS INTERACT WITH THE NORADRENERGIC SYSTEM AND I HYPOTHESIZED THAT THEY MAY MEDIATE COGNITIVE IMPROVEMENTS AT THE PREFRONTAL CORTEX THROUGH SUCH INTERACTIONS. MY HYPOTHESIS IS TESTED ON SYNAPTIC PLASTICITY IN THE RAT HIPPOCAMPAL-PREFRONTAL CORTICAL PATHWAY AND WORKING MEMORY PERFORMANCE IN A WATER MAZE TASK. FIRST, I ESTABLISHED THAT NORADRENALINE CAN AFFECT LONG-TERM POTENTIATION IN THE HIPPOCAMPAL-PREFRONTAL CORTICAL PATHWAY. NEXT, I DEMONSTRATED THE BENEFICIAL EFFECTS OF RISPERIDONE, AN ATYPICAL DRUG, ON WORKING MEMORY PERFORMANCE IN THE WATER MAZE AND ALSO SHOWED THAT BETA-ADRENOCEPTOR ANTAGONIST COULD BLOCK THE IMPROVEMENTS. FINALLY, I SHOWED