Kuzmin A, Johansson B, Zvartau E E, Fredholm B B
Department of Pharmacology, Pavlov Medical University, St. Petersburg, Russia.
J Pharmacol Exp Ther. 1999 Aug;290(2):535-42.
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.
将未接触过药物的DBA/2小鼠训练为通过鼻触来静脉内自我注射可卡因（40微克/千克/次输注）。接受可卡因响应性注射的小鼠（实验组）的鼻触反应次数高于配对对照组或接受响应性盐水注射的动物。在训练期（可卡因或盐水自我给药）24小时后，给小鼠腹腔注射盐水、可卡因、咖啡因、1,3 - 二丙基 - 8 - 环戊基黄嘌呤（DPCPX）、8 - 环戊基茶碱（8 - CPT）、5 - 氨基 - 7 -（2 - 苯乙基）2 -（2 - 呋喃基）- 吡唑并[4,3 - e] - 1,2,4 - 三唑并[1,5 - c]嘧啶（SCH 58261）或9 - 氯 - 2（2 - 呋喃基）[1,2,4]三唑并[1,5 - c]喹唑啉 - 5 - 胺（CGS 15943），然后将它们再次放入与训练期完全相同的操作性实验箱中，但不进行响应性静脉内输注。盐水注射在实验组和配对对照组动物中引发了相似的反应。在单次消退试验中，低剂量的可卡因（5毫克/千克）或咖啡因（3毫克/千克），而非高剂量，在实验组中比在配对对照组中产生了更大的反应。腺苷A(1)受体拮抗剂DPCPX和8 - CPT以及非选择性拮抗剂CGS 15943以剂量依赖性方式部分重现了低剂量咖啡因对可卡因相关行为的影响，并且在消退实验中未改变配对对照组小鼠的鼻触活动。相比之下，腺苷A(2A)拮抗剂SCH 58261，在剂量高于1毫克/千克时，在实验组和配对对照组动物中同等程度地降低了鼻触活动。这证实了来自不同药理学类别的药物（腺苷受体拮抗剂）可以诱导与原始自我给药药物（间接多巴胺受体激动剂）的作用相似的行为变化。数据还表明，咖啡因对可卡因寻求行为的影响可能与与腺苷A(1)受体而非A(2A)受体的相互作用有关。
