Caffeine, acting on adenosine A(1) receptors, prevents the extinction of cocaine-seeking behavior in mice.
Drug-naive DBA/2 mice were trained to self-administer cocaine (40 microgram/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 A(1)-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 A(2A) 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 A(1) receptors, but not A(2A) receptors.
Department of Pharmacology, Pavlov Medical University, St. Petersburg, Russia.
A
A
Kuzmin
B
B
Johansson
E E
EE
Zvartau
B B
BB
Fredholm
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D012201:Reward; D015819:Substance Abuse, Intravenous / Q000523:psychology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D011799:Quinazolines; D014230:Triazoles; D014970:Xanthines; C053907:8-cyclopentyl-1,3-dimethylxanthine; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D003042:Cocaine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine