Selective effects of the D1 dopamine receptor agonist, SKF 38393, on behavior maintained by cocaine injection in squirrel monkeys
- 47 Downloads
The effects of the dopamine receptor D1 partial agonist, SKF 38393, on behavior maintained by cocaine was assessed in squirrel monkeys (Saimiri sciureus). One group of subjects was trained to press a key under a fixed-ratio 30-response schedule of cocaine injection; when green stimulus lamps were illuminated each 30th response produced an injection (17 µg/kg) followed by a 1-min period during which the lights were out and responses had no scheduled consequences. Another group of squirrel monkeys was trained under an identical schedule with food reinforcement. SKF 38393 produced dose-related decreases in rates of responding maintained by either cocaine injection or food presentation. Rates of responding maintained by cocaine were decreased to a greater extent than those maintained by food. The ED50 value for SKF 38393 for responding maintained by cocaine was 2.53 mg/kg (95% CL: 1.22–5.23), whereas that value was 15.63 mg/kg (95% CL: 2.83–86.33) for responding maintained by food. Rates of responding maintained by cocaine were an inverted-U-shaped function of dose. Pretreatment with 3.0 mg/kg SKF 38393 shifted the ascending limb of the cocaine dose-effect curve to the right. These findings suggest that indirect D1-receptor activation plays a role in the reinforcing effects of cocaine, and that drugs acting at D1 receptors may show promise as therapeutic agents in the treatment of cocaine abuse.
Key wordsCocaine Self administration D1 dopamine agonists SKF 38393 Reinforcement Squirrel monkeys
Unable to display preview. Download preview PDF.
- Barrett RL, Appel JB (1989) Effects of stimulation and blockage of dopamine receptor subtypes on the discriminative stimulus properties of cocaine. Psychopharmacology 99:13–16Google Scholar
- Callahan PM, Appel JB, Cunningham KA (1991) Dopamine D1 and D2 mediation of the discriminative stimulus properties ofd-amphetamine and cocaine. Psychopharmacology 103:50–55Google Scholar
- Jaffe JH (1990) Drug addiction and drug abuse. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds) Goodman and Gilman's, The pharmacological basis of therapeutics. Pergamon Press, New York, pp 522–573Google Scholar
- Katz JL (1989) Drugs as reinforcers: pharmacological and behavioral factors. In: Liebman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Oxford University Press, Oxford, pp 164–213Google Scholar
- Witkin JM (1992) Pharmacotherapy of cocaine abuse: preclinical development. Neurosci Biobehav Rev (in press)Google Scholar
- Witkin JM, Katz JL (1992) Preclinical assessment of cocaine toxicity: Mechanisms and pharmacotherapy. In: Sorer H (ed) Cocaine overdose. NIDA Research Monograph, US Gov't Printing Office, Washington, DC (in press)Google Scholar