The behavioral economics of drug self-administration: A review and new analytical approach for within-session procedures

RationaleBehavioral–economic demand curve analysis offers several useful measures of drug self-administration. Although generation of demand curves previously required multiple days, recent within-session procedures allow curve construction from a single 110-min cocaine self-administration session, making behavioral–economic analyses available to a broad range of self-administration experiments. However, a mathematical approach of curve fitting has not been reported for the within-session threshold procedure.ObjectivesWe review demand curve analysis in drug self-administration experiments and provide a quantitative method for fitting curves to single-session data that incorporates relative stability of brain drug concentration.MethodsSprague–Dawley rats were trained to self-administer cocaine, and then tested with the threshold procedure in which the cocaine dose was sequentially decreased on a fixed ratio-1 schedule. Price points (responses/mg cocaine) outside of relatively stable brain cocaine concentrations were removed before curves were fit. Curve-fit accuracy was determined by the degree of correlation between graphical and calculated parameters for cocaine consumption at low price (Q0) and the price at which maximal responding occurred (Pmax).ResultsRemoving price points that occurred at relatively unstable brain cocaine concentrations generated precise estimates of Q0 and resulted in Pmax values with significantly closer agreement with graphical Pmax than conventional methods.ConclusionThe exponential demand equation can be fit to single-session data using the threshold procedure for cocaine self-administration. Removing data points that occur during relatively unstable brain cocaine concentrations resulted in more accurate estimates of demand curve slope than graphical methods, permitting a more comprehensive analysis of drug self-administration via a behavioral–economic framework.

[1]  Wolfram Schultz,et al.  Effects of expectations for different reward magnitudes on neuronal activity in primate striatum. , 2003, Journal of neurophysiology.

[2]  S R Hursh,et al.  Economic concepts for the analysis of behavior. , 1980, Journal of the experimental analysis of behavior.

[3]  A. Odum,et al.  Nicotine gum as a substitute for cigarettes: a behavioral economic analysis , 2000, Behavioural pharmacology.

[4]  M. Weed,et al.  Choice between cocaine and food in a discrete-trials procedure in monkeys: a unit price analysis , 1997, Psychopharmacology.

[5]  B. J. Betts,et al.  Non-commercial Research and Educational Use including without Limitation Use in Instruction at Your Institution, Sending It to Specific Colleagues That You Know, and Providing a Copy to Your Institution's Administrator. All Other Uses, Reproduction and Distribution, including without Limitation Comm , 2006 .

[6]  N. Petry.  A behavioral economic analysis of polydrug abuse in alcoholics: asymmetrical substitution of alcohol and cocaine. , 2001, Drug and alcohol dependence.

[7]  R. See,et al.  A comparison of economic demand and conditioned-cued reinstatement of methamphetamine-seeking or food-seeking in rats , 2011, Behavioural pharmacology.

[8]  J. B. Justice,et al.  Differences in the Pharmacokinetics of Cocaine in Naive and Cocaine‐Experienced Rats , 1991, Journal of neurochemistry.

[9]  Steven R Hursh,et al.  Economic demand and essential value. , 2008, Psychological review.

[10]  W. Bickel,et al.  Deconstructing relative reinforcing efficacy and situating the measures of pharmacological reinforcement with behavioral economics: a theoretical proposal , 2000, Psychopharmacology.

[11]  W. Bickel,et al.  Toward a behavioral economic understanding of drug dependence: delay discounting processes. , 2001, Addiction.

[12]  E. Oleson,et al.  A novel IV cocaine self-administration procedure in rats: differential effects of dopamine, serotonin, and GABA drug pre-treatments on cocaine consumption and maximal price paid , 2011, Psychopharmacology.

[13]  E. Oleson,et al.  Cocaine self-administration in rats: threshold procedures. , 2012, Methods in molecular biology.

[14]  Gary Aston-Jones,et al.  Orexin/hypocretin signaling at the orexin 1 receptor regulates cue‐elicited cocaine‐seeking , 2009, The European journal of neuroscience.

[15]  W K Bickel,et al.  Polydrug abuse in heroin addicts: a behavioral economic analysis. , 1998, Addiction.

[16]  Mikhail N. Koffarnus,et al.  Individual differences in discount rate are associated with demand for self‐administered cocaine, but not sucrose , 2013, Addiction biology.

[17]  D Shurtleff,et al.  A cost-benefit analysis of demand for food. , 1988, Journal of the experimental analysis of behavior.

[18]  H. Davies,et al.  Effect of HD-23, a potent long acting cocaine-analog, on cocaine self-administration in rats , 2003, Psychopharmacology.

[19]  Udo Albus,et al.  Book Review: Guide for the Care and use of Laboratory Animals , 1998 .

[20]  H. Sumnall,et al.  A behavioural economic analysis of alcohol, amphetamine, cocaine and ecstasy purchases by polysubstance misusers. , 2004, Drug and alcohol dependence.

[21]  S. Hursh,et al.  Relative reinforcing effects of three opioids with different durations of action. , 2002, The Journal of pharmacology and experimental therapeutics.

[22]  Matthew W. Johnson,et al.  Substitutes for tobacco smoking: a behavioral economic analysis of nicotine gum, denicotinized cigarettes, and nicotine-containing cigarettes. , 2004, Drug and alcohol dependence.

[23]  J. McGeary,et al.  Behavioral economic analysis of cue-elicited craving for alcohol. , 2010, Addiction.

[24]  S R Hursh,et al.  Relative reinforcing strength of three N-methyl-D-aspartate antagonists with different onsets of action. , 2002, The Journal of pharmacology and experimental therapeutics.

[25]  B. Pitt.  Psychopharmacology , 1968, Mental Health.

[26]  W. Bickel,et al.  The Behavioral Economics and Neuroeconomics of Reinforcer Pathologies: Implications for Etiology and Treatment of Addiction , 2011, Current psychiatry reports.

[27]  James MacKillop,et al.  Alcohol demand, delayed reward discounting, and craving in relation to drinking and alcohol use disorders. , 2010, Journal of abnormal psychology.

[28]  T. J. Breen,et al.  Biostatistical Analysis (2nd ed.). , 1986 .

[29]  S. Hursh,et al.  Essential value of cocaine and food in rats: tests of the exponential model of demand , 2008, Psychopharmacology.

[30]  Sara R. Jones,et al.  The hypocretin–orexin system regulates cocaine self‐administration via actions on the mesolimbic dopamine system , 2010, The European journal of neuroscience.

[31]  A. Newman,et al.  Assessment of Reinforcing Effects of Benztropine Analogs and Their Effects on Cocaine Self-Administration in Rats: Comparisons with Monoamine Uptake Inhibitors , 2009, Journal of Pharmacology and Experimental Therapeutics.

[32]  Serge H. Ahmed,et al.  Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption , 2008, Neuropsychopharmacology.

[33]  W. Bickel,et al.  Modeling drug consumption in the clinic using simulation procedures: demand for heroin and cigarettes in opioid-dependent outpatients. , 1999, Experimental and clinical psychopharmacology.

[34]  A. Rowan.  Guide for the Care and Use of Laboratory Animals , 1979 .

[35]  Steven R. Hursh,et al.  Demand for cocaine and food over time , 2008, Pharmacology Biochemistry and Behavior.

[36]  G. Madden,et al.  A comparison of measures of relative reinforcing efficacy and behavioral economics: cigarettes and money in smokers. , 1999, Behavioural pharmacology.

[37]  Serge H. Ahmed,et al.  A critical transition in cocaine self-administration: behavioral and neurobiological implications , 2007, Psychopharmacology.

[38]  M. Carroll,et al.  A comparison of progressive ratio schedules versus behavioral economic measures: effect of an alternative reinforcer on the reinforcing efficacy of phencyclidine , 1997, Psychopharmacology.

[39]  L. Diergaarde,et al.  Poor impulse control predicts inelastic demand for nicotine but not alcohol in rats , 2012, Addiction biology.

[40]  A. Silberberg,et al.  Demand for food and cocaine in Fischer and Lewis rats. , 2009, Behavioral neuroscience.

[41]  Behavioral economics (Editorial). , 1995, Journal of the experimental analysis of behavior.

[42]  R. Niaura,et al.  Behavioral economic analysis of withdrawal- and cue-elicited craving for tobacco: an initial investigation. , 2012, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[43]  S. Hursh.  Behavioral economics of drug self-administration and drug abuse policy. , 1991, Journal of the experimental analysis of behavior.

[44]  R. Meisch,et al.  Relative reinforcing effects of different doses of orally delivered cocaine. , 1995, Drug and alcohol dependence.

[45]  G F Koob,et al.  Transition from moderate to excessive drug intake: change in hedonic set point. , 1998, Science.

[46]  J. Woods,et al.  A behavioral economic analysis of cocaine and remifentanil self-administration in rhesus monkeys , 2007, Psychopharmacology.

[47]  James MacKillop,et al.  Reliability and validity of a demand curve measure of alcohol reinforcement. , 2009, Experimental and clinical psychopharmacology.

[48]  S. Hursh,et al.  The economics of drug abuse: a quantitative assessment of drug demand. , 2005, Molecular interventions.

[49]  E. Oleson,et al.  Behavioral Economic Assessment of Price and Cocaine Consumption Following Self-Administration Histories which Produce Escalation of Either Final Ratios or Intake , 2008, Neuropsychopharmacology.

[50]  C. Padoa-Schioppa,et al.  Neurons in the orbitofrontal cortex encode economic value , 2006, Nature.

[51]  G. Winger.  Fixed-Ratio and Time-Out Changes on Behavior Maintained by Cocaine or Methohexital in Rhesus Monkeys: 2. Behavioral Economic Analysis , 1993 .

[52]  S. H. Ahmed,et al.  Long-lasting increase in the set point for cocaine self-administration after escalation in rats , 1999, Psychopharmacology.

[53]  Richard J. Cebula,et al.  A Cost Benefit Analysis of Voting , 2002 .

[54]  James MacKillop,et al.  Validity of a demand curve measure of nicotine reinforcement with adolescent smokers. , 2011, Drug and alcohol dependence.

[55]  Wolfram Schultz,et al.  Reward Magnitude Coding in Primate Amygdala Neurons , 2010, Journal of neurophysiology.

[56]  S R Hursh,et al.  Normalized demand for drugs and other reinforcers. , 1995, Journal of the experimental analysis of behavior.

[57]  E. Oleson,et al.  The Motivation to Self-Administer is Increased After a History of Spiking Brain Levels of Cocaine , 2012, Neuropsychopharmacology.

[58]  D. McCann,et al.  Drugs of abuse: management of intoxication and antidotes. , 2010, EXS.

[59]  W. Schultz,et al.  Adaptive Coding of Reward Value by Dopamine Neurons , 2005, Science.

[60]  M Iaccarino,et al.  A cost/benefit analysis , 2000, EMBO reports.

[61]  S R Hursh,et al.  Relative Reinforcing Effects of Cocaine, Remifentanil, and Their Combination in Rhesus Monkeys , 2006, Journal of Pharmacology and Experimental Therapeutics.