title: Escalation patterns of varying periods of heroin access.
abstract: The prevalence of opioid abuse and dependence has been on the rise in just the past few years. Animal studies indicate that extended access to heroin produces escalation of intake over time, whereas stable intake is observed under limited-access conditions. Escalation of drug intake has been suggested to model the transition from controlled drug use to compulsive drug seeking and taking. Here, we directly compared the pattern of heroin intake in animals with varying periods of heroin access. Food intake was also monitored over the course of escalation. Rats were allowed to lever press on a fixed-ratio 1 schedule of reinforcement to receive intravenous infusions of heroin for 1, 6, 12, or 23h per day for 14 sessions. The results showed that heroin intake in the 12 and 23h groups markedly increased over time, whereas heroin intake in the 1h group was stable. The 6h group showed a significant but modest escalation of intake. Total heroin intake was similar in the 12 and 23h groups, but the rate of heroin self-administration was two-fold higher in the 12h group compared with the 23h group. Food intake decreased over sessions only in the 12h group. The 12 and 23h groups showed marked physical signs of naloxone-precipitated withdrawal. These findings suggest that 12h heroin access per day may be the optimal access time for producing escalation of heroin intake. The advantages of this model and the potential relevance for studying drug addiction are discussed.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA92037, USA.
authors.forename: Leandro F
authors.initials: LF
authors.lastname: Vendruscolo
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schlosburg
authors.forename: Kaushik K
authors.initials: KK
authors.lastname: Misra
authors.forename: Scott A
authors.initials: SA
authors.lastname: Chen
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Greenwell
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior; D003932:Heroin / Q000008:administration & dosage*; D006556:Heroin Dependence / Q000209:etiology* / Q000523:psychology*; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000523:psychology; D013997:Time Factors
chemical_list: D009270:Naloxone; D003932:Heroin