Heroin self-administration under a second-order schedule of reinforcement: acquisition and maintenance of heroin-seeking behaviour in rats.
BACKGROUND
Second-order schedules of heroin self-administration provide a method of measuring heroin-seeking behaviour independently of the effects of the drug on motor behaviour and of investigating the role of heroin-associated stimuli in such heroin-seeking behaviour.


OBJECTIVE
These experiments 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-associated stimuli in the maintenance of heroin-seeking behaviour under a second-order schedule of reinforcement.


METHODS
Heroin i.v. self-administration (0.04 mg/infusion) was initially contingent upon a lever press, and each infusion was paired with presentation of a 20-s light-conditioned stimulus (CS). Following acquisition of heroin self-administration, the response requirement was progressively increased so that, ultimately, responding was maintained 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/infusion) and pre-treatment with the mu-opiate receptor antagonist, naloxone, on responding under a FI15(FR5:S) schedule were investigated. In addition, the role of the heroin-associated CS on responding was assessed by measuring the effects of omitting the CS during heroin-seeking behaviour and during extinction of responding, as well as the effect of CS presentation on the reinstatement of heroin-seeking behaviour following extinction.


RESULTS
A second-order schedule of heroin self-administration was established. There were no clear effects on heroin-seeking behaviour of increasing or decreasing the dose of heroin. Although no effect of naloxone pre-treatment was seen on heroin-seeking behaviour during the first, drug-free interval of responding, an extinction-like pattern of responding was seen in that interval during subsequent sessions. Omission of the light CS resulted in a reduction in levels of responding for i.v. heroin, indicating its role in maintaining heroin-seeking behaviour. However, under extinction conditions, response-contingent CS presentations did not affect the rate of extinction, nor did non-contingent presentations of the CS following extinction reinstate heroin-seeking behaviour.


CONCLUSIONS
These experiments have established a method of measuring heroin-seeking behaviour in rats by adopting a second-order schedule of i.v. heroin self-administration. The results indicate a relatively weak impact of discrete, heroin-associated cues on heroin-seeking behaviour relative to cocaine-seeking behaviour studied under similar conditions.
Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
H L
HL
Alderson
T W
TW
Robbins
B J
BJ
Everitt
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D003932:Heroin / Q000008:administration & dosage* / Q000494:pharmacology*; D006556:Heroin Dependence / Q000523:psychology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D012055:Reinforcement Schedule; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D003932:Heroin; D003042:Cocaine