DOES LEARNED HELPLESSNESS INDUCTION BY HALOPERIDOL INVOLVE SEROTONIN MEDIATION

Learned helplessness (LH) is a behavioral depression following inescap able stress. Helpless behavior was induced in naive rats by the dopami ne D, receptor blocker haloperidol (HDL) in a dose-dependent manner, w ith the greatest effects seen at 20 mg/kg (IF). Rats were tested 24 h after injection. Haloperidol (IF) increased release of serotonin (5-HT ) in medial prefrontal cortex (MPC) as measured by in vivo microdialys is. Perfusion of HDL through the probe in MPC caused increased cortica l 5-HT release, as did perfusion of both dopamine and the dopamine ago nist apomorphine. Our previous work found that increased 5-HT release in MPC correlates with the development of LH. The present work suggest s that increased DA release in MPC, known to occur with both inescapab le stress and with HDL, may play a necessary but not sufficient role i n the development of LH. Also, this suggests that increased DA activit y in MPC leads to increased 5-HT release in MPC and to subsequent beha vioral depression.