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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

Authors
  • Arroyo, Mercedes1
  • Markou, Athina2
  • Robbins, Trevor W.1
  • Everitt, B. J.1
  • 1 Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK, GB
  • 2 Department of Neuropharmacology, The Scripps Research Institute, 10666 N. Torrey Pines Road, La Jolla, CA 92037, USA, US
Type
Published Article
Journal
Psychopharmacology
Publication Date
Dec 01, 1998
Volume
140
Issue
3
Pages
331–344
Identifiers
DOI: 10.1007/s002130050774
Source
Springer Nature
Keywords
License
Yellow

Abstract

Second order schedules of IV cocaine reinforcement in rats provide a reliable method for evaluating the effects of conditioned stimuli on cocaine-seeking behaviour, and for measuring the motivational aspects of cocaine reinforcement. In the procedure established here, each infusion of cocaine (0.25 mg/infusion) was initially made contingent on a lever press and was paired with a 20-s light conditioned stimulus (CS). When rats acquired stable rates of cocaine self-administration, the response requirement for cocaine was increased progressively to a second-order schedule of the type FI15 min(FR10:S), whereby the IV cocaine infusion was self-administered following the completion of the first FR10 responses (and CS presentation) after a 15-min fixed interval (FI) had elapsed. Evaluation of the animals’ responding during the first, drug-free interval of each daily session provided a measure of cocaine-seeking behaviour, independent of other pharmacological effects of the self-administered drug. Thus, a dose-response study (dose range: 0.083, 0.25 and 0.50 mg/infusion) revealed that responding under this schedule during the initial, drug-free interval changed monotonically with dose, whereas an inverse relationship between cocaine dose and response level tended to appear during the rest of the session, after rats had self-administered the drug. Responding under this schedule was also shown to occur under the control of the CS, which had acquired conditioned reinforcing properties. Thus, a decrease in responding and an increase in the latency to initiate responding followed the omission of the CS for 3 consecutive days. In addition, extinction of cocaine-seeking behaviour was slower when contingent CS presentations occurred compared to extinction when the CS was not present. Furthermore, the reinstatement of responding for cocaine, which followed a brief period of non-contingent CS presentations, was retarded when this conditioned reinforcer had been extinguished together with cocaine. Finally, cocaine-seeking behaviour decreased markedly for the first 6 h that followed a 12-h period of continuous access to cocaine, when compared to responding 6 h after a 90-min session of limited access to the drug. Responding subsequently increased to baseline levels within 72 h. These results emphasise the utility of second-order schedules for studying drug-seeking behaviour and the importance of drug-associated cues in maintaining such responding for cocaine.

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