Abstract
Drugs that decrease drug-maintained responding at doses that do not decrease other behaviors in animals may be suitable candidates for development as medications to treat drug abuse in humans. The present study examined whether this effect could be obtained with phentermine, a drug that has been reported to decrease cocaine intake in humans. Rhesus monkeys were trained under multiple fixed-ratio 30-response schedules of food and i.v. cocaine delivery. Phentermine was always given as a slow, i.v. infusion. Acute treatment with phentermine (0.3–10 mg/kg) decreased cocaine-maintained responding at doses that did not decrease, or decreased less, food-maintained responding for each of three unit doses of cocaine (10–100 μg/kg/injection). Subacute treatment with phentermine (3 or 5.6 mg/kg, daily) also decreased cocaine-maintained responding more than food-maintained responding. After subacute treatment was terminated, rates of cocaine-maintained responding generally recovered to levels comparable to those seen during untreated control sessions. Phentermine (0.3–3 mg/kg) did not generally increase responding associated with a very low (1 μg/kg/injection) unit dose of cocaine, suggesting that the decrease in cocaine-maintained responding at higher unit doses was not the result of a leftward shift in the cocaine unit dose-effect function. Phentermine (0.1–3 mg/kg) decreased responding maintained by 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine (GBR 12909) (30 μg/kg/injection) at doses similar to those that decreased food-maintained responding. These results show that phentermine is effective in decreasing cocaine self-administration and suggest that it may be an effective medication for cocaine abuse.
Footnotes
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Send reprint requests to: Dr. John R. Glowa, Professor of Pharmacology and Psychiatry, Department of Pharmacology and Therapeutics, Louisiana State University Medical School in Shreveport, 1501 Kings Highway, P.O. Box 33932, Shreveport, LA 71103-3932. E-mail:jglowa{at}lsumc.edu
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↵1 This work was supported, in part, by a National Institute on Drug Abuse Interagency Agreement no. RA-ND-94 to 24 and by National Institute on Drug Abuse Grant RO1 DA09820 (J.R.G., Principal Investigator). Portions of the data were presented at the Society for Neuroscience Meeting, Miami, FL, 1994. All animal procedures conformed to the Guide for Care and Use of Laboratory Animals endorsed by the National Institutes of Health.
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↵2 Clinical Psychopharmacology Section, National Institute on Drug Abuse/National Institutes of Health Addiction Research Center, Baltimore, MD.
- Abbreviations:
- GBR 12909
- 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-[3-phenylpropyl] piperazine
- CFT
- 2-β-carboxymethoxy-3-β-(4-fluorophenyl)tropane
- DA
- dopamine
- FR
- fixed-ratio
- mult
- multiple
- TO
- time-out
- LH
- limited hold
- resp/sec
- responses per second
- Received March 6, 1997.
- Accepted July 28, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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