Dose escalation and dose preference in extended-access heroin self-administration in Lewis and Fischer rats

Rationale A genetic component may be involved in different stages of the progression of drug addiction. Heroin users escalate unit doses and frequency of self-administration events over time. Rats that self-administer drugs of abuse over extended sessions escalate the amount of drug infused over days. Objectives Using a recently developed model of extended-access self-administration allowing for subject-controlled dose escalation of the unit dose, thus potentially escalating the unit dose and number of infusions, we compared for the first time two genetically different inbred rat strains, Fischer and Lewis. Methods Extended (18 h/day) self-administration lasted for 14 days. Rats had access to two active levers associated with two different unit doses of heroin. If a rat showed preference for the higher unit dose, then the available doses were escalated in the following session. Four heroin unit doses were available (20, 50, 125, 250 mu g/kg per infusion). Results Fischer rats did not escalate the unit dose of heroin self-administered; daily amount of heroin administered remained low, with a mean daily intake of 1.27 +/- 0.22 mg/kg per session. In marked contrast, Lewis rats escalated the total daily amount of heroin self-administered from 3.94 +/- 0.82 mg/kg on day 1 to 8.95 +/- 2.2 mg/kg on day 14; almost half of the subjects preferred a higher heroin dose than Fischer rats. Conclusion These data are consistent with the hypothesis that Lewis rats are prone to opiate taking and escalation, and are in agreement with our previous data obtained with cocaine.