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Effects of chronic d-amphetamine administration on the reinforcing strength of cocaine in rhesus monkeys.
Psychopharmacology (Berl). 2010 May; 209(4):375-82.P

Abstract

RATIONALE

Agonist medications have been proven effective in treating opioid and nicotine dependence; results from clinical studies suggest that the indirect dopamine agonist d-amphetamine may reduce cocaine abuse. In preclinical studies, chronic d-amphetamine treatment decreased ongoing cocaine self-administration.

OBJECTIVES

The present study extended previous results by determining effects of chronic d-amphetamine treatment on the reinforcing strength of cocaine under conditions in which access to cocaine was suspended during d-amphetamine treatment.

METHODS

Daily operant conditioning sessions consisted of morning access to food pellets delivered under a 50-response fixed-ratio schedule and evening access to cocaine (0.005-0.48 mg/kg per injection, i.v.) under a progressive-ratio schedule. After responding maintained by 0.045 mg/kg per injection cocaine stabilized, self-administration sessions were suspended and d-amphetamine (0.01-0.1 mg/kg per hr, i.v.) was administered continuously for 5 days. On the following day, d-amphetamine treatment was discontinued and daily self-administration sessions resumed.

RESULTS

Following termination of d-amphetamine treatment, food- and cocaine-maintained responding was decreased in a dose-related manner. Decreases in the reinforcing strength of cocaine were larger and lasted longer than effects on food reinforcement. However, cocaine self-administration was unaltered if 6 days elapsed between discontinuation of d-amphetamine treatment and the next cocaine self-administration session.

CONCLUSIONS

The necessity of a self-administration session in the presence of d-amphetamine suggests that the protracted decrease in cocaine self-administration may be a manifestation of behavioral tolerance. Regarding treatment of cocaine dependence, data suggest that prolonged d-amphetamine treatment may be necessary to produce a sustained reduction in the reinforcing effects of cocaine.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Center for the Neurobiology of Addiction Treatments (CNAT), Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20217052

Citation

Czoty, Paul W., et al. "Effects of Chronic D-amphetamine Administration On the Reinforcing Strength of Cocaine in Rhesus Monkeys." Psychopharmacology, vol. 209, no. 4, 2010, pp. 375-82.
Czoty PW, Martelle JL, Nader MA. Effects of chronic d-amphetamine administration on the reinforcing strength of cocaine in rhesus monkeys. Psychopharmacology (Berl). 2010;209(4):375-82.
Czoty, P. W., Martelle, J. L., & Nader, M. A. (2010). Effects of chronic d-amphetamine administration on the reinforcing strength of cocaine in rhesus monkeys. Psychopharmacology, 209(4), 375-82. https://doi.org/10.1007/s00213-010-1807-x
Czoty PW, Martelle JL, Nader MA. Effects of Chronic D-amphetamine Administration On the Reinforcing Strength of Cocaine in Rhesus Monkeys. Psychopharmacology (Berl). 2010;209(4):375-82. PubMed PMID: 20217052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of chronic d-amphetamine administration on the reinforcing strength of cocaine in rhesus monkeys. AU - Czoty,Paul W, AU - Martelle,Jennifer L, AU - Nader,Michael A, Y1 - 2010/03/09/ PY - 2010/01/05/received PY - 2010/02/15/accepted PY - 2010/3/11/entrez PY - 2010/3/11/pubmed PY - 2010/7/9/medline SP - 375 EP - 82 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 209 IS - 4 N2 - RATIONALE: Agonist medications have been proven effective in treating opioid and nicotine dependence; results from clinical studies suggest that the indirect dopamine agonist d-amphetamine may reduce cocaine abuse. In preclinical studies, chronic d-amphetamine treatment decreased ongoing cocaine self-administration. OBJECTIVES: The present study extended previous results by determining effects of chronic d-amphetamine treatment on the reinforcing strength of cocaine under conditions in which access to cocaine was suspended during d-amphetamine treatment. METHODS: Daily operant conditioning sessions consisted of morning access to food pellets delivered under a 50-response fixed-ratio schedule and evening access to cocaine (0.005-0.48 mg/kg per injection, i.v.) under a progressive-ratio schedule. After responding maintained by 0.045 mg/kg per injection cocaine stabilized, self-administration sessions were suspended and d-amphetamine (0.01-0.1 mg/kg per hr, i.v.) was administered continuously for 5 days. On the following day, d-amphetamine treatment was discontinued and daily self-administration sessions resumed. RESULTS: Following termination of d-amphetamine treatment, food- and cocaine-maintained responding was decreased in a dose-related manner. Decreases in the reinforcing strength of cocaine were larger and lasted longer than effects on food reinforcement. However, cocaine self-administration was unaltered if 6 days elapsed between discontinuation of d-amphetamine treatment and the next cocaine self-administration session. CONCLUSIONS: The necessity of a self-administration session in the presence of d-amphetamine suggests that the protracted decrease in cocaine self-administration may be a manifestation of behavioral tolerance. Regarding treatment of cocaine dependence, data suggest that prolonged d-amphetamine treatment may be necessary to produce a sustained reduction in the reinforcing effects of cocaine. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/20217052/Effects_of_chronic_d_amphetamine_administration_on_the_reinforcing_strength_of_cocaine_in_rhesus_monkeys_ L2 - https://dx.doi.org/10.1007/s00213-010-1807-x DB - PRIME DP - Unbound Medicine ER -