The development of opiate addiction in the rat.

Opiate intake was studied in rats, which were given free choice between water and etonitazene (ETZ) solutions (2, 4, and 8 mg/l) for 30 weeks. After an abstinence of 19 weeks, the opiate was reoffered. The long-term course of intake could be subdivided in three phases: a period of controlled intake (25 weeks), a period of increasing consumption (week 25-30), and the stage of drug addiction (retest). During controlled intake, environmental and individual variables reversibly influenced ETZ intake (high intake in socially deprived and in subordinate rats, low intake in group-housed and in dominant rats). After 25 weeks of situation-specific intake, the rats spontaneously increased ETZ consumption. In the retest after long-term ETZ-abstinence, their intake was strongly increased compared to both their own intake before and to that of drug-naive controls. ETZ intake could no longer be influenced by environmental, gustatory, or individual factors ("loss of control") indicating opiate addiction. In contrast, rats that have formerly had forced administration by means of a 2 mg/l ETZ solution did not become addicted. Signs of opiate withdrawal, however, occurred in both series of forced and voluntary intake. Principles of the temporal development of opiate addiction are compared with those described previously for ethanol addiction.