Responses to novelty stress in female F344 rats: Effects of age and d-fenfluramine treatment

To elucidate some of the mechanisms underlying the neuroendocrine and neurochemical changes associated with age in female rats, we administered the serotonin (5-HT) releaser and reuptake inhibitor, d-fenfluramine (d-FEN; 0.0 or 0.6 mg/kg/day, PO) for 30-38 days to young (4 month) and old (21 month) F-344 female rats. Animals were placed into a novel open field (OF) for 20 min before sacrifice. Control animals were sacrificed immediately upon removal from their home cage (HC). Old rats exhibited significantly (p < 0.05) less exploratory behavior and a smaller CORT response to OF than young animals. d-FEN treatment had no effect on plasma ACTH and CORT levels or exploratory behavior. The old HC rats had significantly (p < 0.05) higher plasma levels of prolactin (PRL) than the young HC rats. A stress induced increase in PRL secretion was observed in the old rats only, which was attenuated by d-FEN treatment. In the OF groups, both the young and old rats showed elevated medial frontal cortex (MFC) dopamine turnover (DOPAC/DA ratio), but only the young rats exhibited an elevation in norepinephrine (NE) turnover (MHPG/NE ratio). d-FEN treatment blocked the stress-induced increase in NE turnover in the young rats and the increase in DA turnover in the old rats. These data suggest that 5-HT activity could be involved in the age-related changes in the MFC catecholamine and PRL responses to stress in female rats.