Within-session determination of dose-response curves for heroin self-administration in rats: Comparison with between-session determination and effects of naltrexone.
A procedure was employed in the present study to obtain dose-response curves for heroin self-administration within each experimental session. The data generated using this procedure were compared to dose-response data obtained using between-session dose manipulations. The dose of heroin (18, 30, 60 or 100 micrograms/kg/inf) was varied across 4-hourly segments separated by a 20-min time-out period during which heroin was not available. The within-session dose-response procedure yielded data similar to those obtained using between-session dose manipulations when the order of dose presentation was increasing or random. However, the dose-response curve for total drug-intake was flat when the doses were presented in decreasing order. Further analysis of the dose-response curves in the within-session procedure demonstrated that the rate of heroin intake increased in the third and fourth hourly components compared to the first component, suggesting acute tolerance to the reinforcing and/or rate-suppressive effects of heroin. Furthermore, using a random order of dose presentation, administration of 3.0 mg/kg of naltrexone prior to the session shifted the dose-response curve for heroin self-administration 5-fold to the right in the within-session procedure. The data indicate that the within-session dose-response procedure can be used to investigate the pharmacology of heroin self-administration in rodents.
Martin
T J
TJ
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1083, USA.
Walker
L E
LE
Sizemore
G M
GM
Smith
J E
JE
Dworkin
S I
SI
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D003932:Heroin / Q000008:administration & dosage*; D006556:Heroin Dependence / Q000523:psychology*; D008297:Male; D009042:Motivation; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012055:Reinforcement Schedule; D012646:Self Administration
D009292:Narcotic Antagonists; D009271:Naltrexone; D003932:Heroin