Deranged diurnal feeding pattern and altered brain serotonin turnover in heroin-dependent rats

Rats rendered tolerant to and dependent on heroin by administering escalating dosages of heroin from 5 mg/kg-1 to 30 mg/kg-1 s,c, twice daily for 10 days exhibited disrupted diurnal feeding patterns. Daylight food intake was significantly increased, whereas night-time feeding was significantly decreased, as compared with the saline-control group. Growth rate evaluated on the basis of changes in daily body weights was considerably attenuated. The heroin-treated rats showed typical abstinence signs upon naloxone challenge 8 hr after the last heroin challenge. No significant changes were observed in the brain levels of tryptophan, serotonin and 5-hydroxyindoleacetic acid. The formation of newly synthesised 3H-serotonin from 3H-tryptophan was significantly reduced, as evidenced from the decreased specific activity of serotonin. The results obtained in this study indicate that whereas the perturbed diurnal feeding activity cannot be ascribed exclusively to altered central serotonergic mechanism, chronic heroin treatment appears to decrease the rate of serotonin via a negative feedback loop.