Influence of a conditioned light stimulus on cocaine self-administration in rats

Abstract. Rationale: A number of studies have suggested that the continued presentation of stimuli associated with cocaine may contribute to drug-seeking and drug-taking. The influence of conditioned stimuli on the maintenance of self-administration has not, however, been systematically investigated. Objectives: This study was designed to determine whether omission of a stimulus that had been paired with self-administered cocaine would influence the maintenance of cocaine self-administration and whether the effect was dependent on cocaine dose or session length. Methods: During self-administration training, self-administered cocaine infusions were always paired with the illumination of a light. On test days, self-administered cocaine was delivered either with or without the cocaine-associated cue. For one group of rats, responding maintained by cocaine (0.50 mg/kg per infusion) was measured during daily 18-h sessions. For other groups, responding maintained by additional doses of cocaine (0.125, 0.25, or 1.0 mg/kg per infusion) was measured during daily 8-h sessions. For a final group, daily test sessions (4–5 h) produced the dose-effect curve (0.015–1.0 mg/kg per infusion) by repeatedly reducing the cocaine dose from a starting dose of 1.0 mg/kg per infusion. Results: Removal of the light cue decreased cocaine self-administration. The magnitude of this effect was dependent on the dose of self-administered cocaine and on the test session duration. Greater decrements in responding were produced as session length increased or when low doses of cocaine were self-administered. Conclusions: These findings demonstrate that in the absence of a cocaine-associated stimulus, cocaine self-administration is attenuated and that maintenance of cocaine self-administration is maximally affected by the presence or absence of the conditioned stimulus when the self-administered dose is low and/or when session duration is long.

[1]  Robert E. Hampson,et al.  Firing patterns of nucleus accumbens neurons during cocaine self-administration in rats , 1993, Brain Research.

[2]  T. Shippenberg,et al.  Effects of the Kappa-opioid Receptor Agonist, U69593, on the Development of Sensitization and on the Maintenance of Cocaine Self-administration , 2001, Neuropsychopharmacology.

[3]  T. Robbins,et al.  Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine , 1998, Psychopharmacology.

[4]  Michael W. Emmett-Oglesby,et al.  Parallel processing strategies in the application of microcomputers to the behavioral laboratory , 1985 .

[5]  F. Weiss,et al.  Role for the mesocortical dopamine system in the motivating effects of cocaine. , 1994, NIDA research monograph.

[6]  M. Bardo,et al.  Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens. , 1998, Critical reviews in neurobiology.

[7]  Activation of accumbens cell firing by stimuli associated with cocaine delivery during self‐administration , 2000, Synapse.

[8]  D. Calcagnetti,et al.  Trends in place preference conditioning with a cross-indexed bibliography; 1957–1991 , 1993, Neuroscience & Biobehavioral Reviews.

[9]  R. Peltier,et al.  Supersensitivity to the reinforcing effects of cocaine following 6-hydroxydopamine lesions to the medial prefrontal cortex in rats , 1991, Brain Research.

[10]  N. Mello,et al.  Preclinical Evaluation of Pharmacotherapies for Treatment of Cocaine and Opioid Abuse Using Drug Self-Administration Procedures , 1996, Neuropsychopharmacology.

[11]  S. Schenk,et al.  Sensitization to Cocaine's Reinforcing Effects Produced by Various Cocaine Pretreatment Regimens in Rats , 2000, Pharmacology Biochemistry and Behavior.

[12]  T. Robbins,et al.  Effects of medial prefrontal or anterior cingulate cortex lesions on responding for cocaine under fixed-ratio and second-order schedules of reinforcement in rats , 1997, Psychopharmacology.

[13]  M. West,et al.  Phasic Firing of Single Neurons in the Rat Nucleus Accumbens Correlated with the Timing of Intravenous Cocaine Self-Administration , 1996, The Journal of Neuroscience.

[14]  Jeffrey W Grimm,et al.  Dissociation of Primary and Secondary Reward-Relevant Limbic Nuclei in an Animal Model of Relapse , 2000, Neuropsychopharmacology.

[15]  R. T. Kelleher,et al.  Enhancement of drug-seeking behavior by environmental stimuli associated with cocaine or morphine injections , 1979, Neuropharmacology.

[16]  R. Ehrman,et al.  Classically conditioned responses in opioid and cocaine dependence: a role in relapse? , 1988, NIDA research monograph.

[17]  Y Hatano,et al.  Acute tolerance development to the cardiovascular and subjective effects of cocaine. , 1985, The Journal of pharmacology and experimental therapeutics.

[18]  R. Carelli,et al.  Evidence That Separate Neural Circuits in the Nucleus Accumbens Encode Cocaine Versus “Natural” (Water and Food) Reward , 2000, The Journal of Neuroscience.

[19]  R. Wise Neural mechanisms of the reinforcing action of cocaine. , 1984, NIDA research monograph.

[20]  R. A. Fuchs,et al.  Fos Protein Expression and Cocaine-Seeking Behavior in Rats after Exposure to a Cocaine Self-Administration Environment , 2000, The Journal of Neuroscience.

[21]  S A Deadwyler,et al.  A comparison of nucleus accumbens neuronal firing patterns during cocaine self-administration and water reinforcement in rats , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  J. Taylor,et al.  Enhanced responding for conditioned reward produced by intra-accumbens amphetamine is potentiated after cocaine sensitization , 1999, Psychopharmacology.

[23]  R. Ranaldi,et al.  Initiation, maintenance and extinction of cocaine self-administration with and without conditioned reward , 1996, Psychopharmacology.

[24]  H. Fibiger,et al.  Evidence for conditional neuronal activation following exposure to a cocaine-paired environment: role of forebrain limbic structures , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  F. Weiss ENDURING CONDITIONED REACTIVITY TO COCAINE CUES: EFFECTS ON EXTINGUISHED OPERANT RESPONDING, FOREBRAIN DOPAMINE RELEASE, AND FOS IMMUNOREACTIVITY , 1999 .

[26]  R. Ehrman,et al.  Classical Conditioning in Drug‐Dependent Humans a , 1992, Annals of the New York Academy of Sciences.

[27]  B. Everitt,et al.  Effects of Contingent and Non-Contingent Cocaine on Drug-Seeking Behavior Measured Using a Second-Order Schedule of Cocaine Reinforcement in Rats , 1999, Neuropsychopharmacology.

[28]  C. Bradberry,et al.  Impact of Self-Administered Cocaine and Cocaine Cues on Extracellular Dopamine in Mesolimbic and Sensorimotor Striatum in Rhesus Monkeys , 2000, The Journal of Neuroscience.

[29]  R. Post,et al.  Conditioned increases in mesolimbic dopamine overflow by stimuli associated with cocaine , 1993, Brain Research.

[30]  Mark O West,et al.  Operant behavior during sessions of intravenous cocaine infusion is necessary and sufficient for phasic firing of single nucleus accumbens neurons , 1997, Brain Research.

[31]  D. Calcagnetti,et al.  Continued Trends in the Conditioned Place Preference Literature from 1992 to 1996, Inclusive, with a Cross-Indexed Bibliography , 1998, Neuroscience & Biobehavioral Reviews.

[32]  E. Stein,et al.  Conditioned changes in nucleus accumbens dopamine signal established by intravenous cocaine in rats , 1996, Neuroscience Letters.

[33]  D. J. Spear,et al.  Cocaine and food as reinforcers: effects of reinforcer magnitude and response requirement under second-order fixed-ratio and progressive-ratio schedules. , 1991, Journal of the experimental analysis of behavior.

[34]  R. Carelli,et al.  Nucleus accumbens cell firing during maintenance, extinction, and reinstatement of cocaine self-administration behavior in rats , 2000, Brain Research.

[35]  M. West,et al.  Phasic Firing Time Locked to Cocaine Self-Infusion and Locomotion: Dissociable Firing Patterns of Single Nucleus Accumbens Neurons in the Rat , 1998, The Journal of Neuroscience.