Heroin self-administration under a second-order schedule of reinforcement:acquisition and maintenance of heroin-seeking behaviour in rats

Rationale: Second-order schedules of heroin self-administration provide a m ethod of measuring heroin-seeking behaviour independently of the effects of the drug on motor behaviour and of investigating the role of heroin-associ ated stimuli in such heroin-seeking behaviour. Objectives: These experiment s aimed to establish a second-order schedule of heroin self-administration in rats, similar to that already established in this laboratory for cocaine self-administration and to investigate the role of discrete heroin-associa ted stimuli in the maintenance of heroin-seeking behaviour under a second-o rder schedule of reinforcement. Methods: Heroin i.v. self-administration (0 .04 mg/infusion) was initially contingent upon a lever press, and each infu sion was paired with presentation of a 20-s light-conditioned stimulus (CS) . Following acquisition of heroin self-administration, the response require ment was progressively increased so that, ultimately, responding was mainta ined under a fixed interval (FI) 15 min [fixed ratio (FR)5:S] second-order schedule. The effects of varying the dose of heroin (0.01 mg and 0.08 mg/in fusion) and pre-treatment with the mu -opiate receptor antagonist, naloxone , on responding under a FI15(FRS:S) schedule were investigated. In addition , the role of the heroin-associated CS on responding was assessed by measur ing the effects of omitting the CS during heroin-seeking behaviour and duri ng extinction of responding, as well as the effect of CS presentation on th e reinstatement of heroin-seeking behaviour following extinction. Results: A second-order schedule of heroin self-administration was established. Ther e were no clear effects on heroin-seeking behaviour of increasing or decrea sing the dose of heroin. Although no effect of naloxone pre-treatment was s een on heroin-seeking behaviour during the first, drug-free interval of res ponding, an extinction-like pattern of responding was seen in that interval during subsequent sessions. Omission of the light CS resulted in a reducti on in levels of responding for i.v. heroin, indicating its role in maintain ing heroin-seeking behaviour. However, under extinction conditions, respons e-contingent CS presentations did not affect the rate of extinction, nor di d non-contingent presentations of the CS following extinction reinstate her oin-seeking behaviour. Conclusions: These experiments have established a me thod of measuring heroin-seeking behaviour in rats by adopting a second-ord er schedule of i.v. heroin self-administration. The results indicate a rela tively weak impact of discrete, heroin-associated cues on heroin-seeking be haviour relative to cocaine-seeking behaviour studied under similar conditi ons.