Effects of chronic administration of heroin on rats trained on two food reinforcement schedules.

The effects on behaviour and growth of rats given heroin s.c. every 8-hr, and during withdrawal (saline q.8.h.) were studied. Performance of rats trained on one food-reinforcement schedule (FR-10 or VI-10) was tested every day after one of the injections of saline or heroin. Doses of 0.25 mg/kg/injection heroin hydrochloride were increased stepwise to 32 mg/kg as "behavioural tolerance" developed. Threshold doses which blocked feeding in the first 30 min of testing ranged from 0.75 to 4.0 mg/kg and "tolerance" to 32 mg/kg/injection required from 18-71 + days. Heroin interrupted growth in heavier rats; lighter rats gained like saline-treated controls. Within 48 hr of withdrawal bar-pressing increased but all rats lost weight, were hyperirritable, and had diarrhoea. Thereafter, performance and body weight rose steadily. Administration of heroin at regular intervals over a prolonged period, and withdrawal from it, cause a disruption in behaviour comparable to that reported for morphine.