Escalation patterns of varying periods of heroin access

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2011-06, Vol.98 (4), p.570-574
• Main Authors: Vendruscolo, Leandro F., Schlosburg, Joel E., Misra, Kaushik K., Chen, Scott A., Greenwell, Thomas N., Koob, George F.
• Format: Article
• Language: English
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Animals; Behavior, Animal; Biological and medical sciences; Disease Models, Animal; Drug addiction; Drug-Seeking Behavior; Escalation; Heroin - administration & dosage; Heroin Dependence - etiology; Heroin Dependence - psychology; Heroin self-administration; Humans; Male; Medical sciences; Naloxone - pharmacology; Naloxone-precipitated withdrawal; Opioid dependence; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome - etiology; Substance Withdrawal Syndrome - psychology; Time Factors
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2011.03.004

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 23 h per day for 14 sessions. The results showed that heroin intake in the 12 and 23 h groups markedly increased over time, whereas heroin intake in the 1 h group was stable. The 6 h group showed a significant but modest escalation of intake. Total heroin intake was similar in the 12 and 23 h groups, but the rate of heroin self-administration was two-fold higher in the 12 h group compared with the 23 h group. Food intake decreased over sessions only in the 12 h group. The 12 and 23 h groups showed marked physical signs of naloxone-precipitated withdrawal. These findings suggest that 12 h 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. ► 12 h access per day to heroin produces optimal escalation of heroin intake. ► Escalation of heroin intake is accompanied by concurrent decreases in food intake. ► Extended heroin access produces escalation; limited access produces stable intake. ► Extended access to heroin produces physical signs of opiate dependence.