Abstract
Drug-naive DBA/2 mice were trained to self-administer cocaine (40 μg/kg/infusion) i.v. by nose poking. The number of nose-poke responses was higher in mice receiving response-contingent injections of cocaine (active group) than in yoked controls or in animals receiving response-contingent saline injections. Twenty-four hours after the training session (cocaine or saline self-administration), mice were injected i.p. with saline, cocaine, caffeine, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX), 8-cyclopentyl theophylline (8-CPT), 5-amino-7-(2-phenylethyl)2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261), or 9-chloro-2(2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS 15943) and placed again in exactly the same operant boxes as during the training session but without response-contingent i.v. infusions. Saline injection elicited similar responding in animals from the active group and from the yoked control group. A low dose of cocaine (5 mg/kg) or caffeine (3 mg/kg), but not higher doses, produced greater responding in the active group than in the yoked control group during a single extinction trial. The adenosine A1-receptor antagonists DPCPX and 8-CPT and the nonselective antagonist CGS 15943 partially reproduced the effect of a low dose of caffeine on the cocaine-associated behavior in a dose-dependent manner and did not alter the nose-poke activity of yoked control mice in the extinction experiment. In contrast, the adenosine A2A antagonist SCH 58261, in doses above 1 mg/kg, reduced nose-poke activity equally in active and yoked control animals. This confirms that a drug from a different pharmacological class (adenosine-receptor antagonist) can induce behavior changes similar to the effects of the original self-administered drug (indirect dopamine-receptor agonist). The data also suggest that the effects of caffeine on cocaine-seeking behavior might be related to interaction with adenosine A1receptors, but not A2A receptors.
Footnotes
-
Send reprint requests to: Dr. Bertil B. Fredholm, Section of Molecular Neuropharmacology, Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden. E-mail:Bertil.Fredholm{at}fyfa.ki.se
-
↵1 This work was supported by Physiological Effects of Coffee Committee (PEC), Swedish Medical Research Council (Projects 2553 and 12587), Socialstyrelsens Fonder, the Åke Wiberg Foundation, Magn. Bergvall Foundation, O. E. and Edla Johansson Scientific Foundation, Syskonen Svenssons Fund for Medical Research, and Fredrik and Ingrid Thuring Foundation. A. K. received visiting scientist support from the Karolinska Institute and from the Royal Swedish Academy of Sciences. B. J. was supported by a grant from the Brain Fund.
- Abbreviations:
- DPCPX
- 1,3-dipropyl-8-cyclopentyl xanthine
- 8-CPT
- 8-cyclopentyl theophylline
- SCH 58261
- 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine
- CGS 15943
- 9-chloro-2(2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine
- DMSO
- dimethyl sulfoxide
- Received October 7, 1998.
- Accepted April 22, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|