Winsky L, Harvey J A
J Pharmacol Exp Ther. 1987 Apr;241(1):223-9.
This study examined the effects of caffeine, theophylline and rolipram on the acquisition of conditioned responses in the rabbit and their ability to antagonize the retardant effects of the adenosine analog N6-(L-phenylisopropyl)adenosine (L-PIA) on acquisition. Pavlovian conditioning of nictitating membrane extension was accomplished by pairing the offset of a 800-msec tone- and light-conditioned stimulus with the onset of a 100-msec shock unconditioned stimulus to the skin just lateral to the outer canthus of the eye. L-PIA (5 mumol/kg) retarded the acquisition of conditioned responses to the tone- and light-conditioned stimuli, although theophylline (50-200 mumol/kg), caffeine (3-100 mumol/kg) and rolipram (0.03-3.0 mumol/kg) had no effect. The highest dose of caffeine used (300 mumol/kg) produced a small but significant enhancement of conditioned response acquisition in two of four experiments. The two adenosine antagonists theophylline (200 mumol/kg) and caffeine (300 mumol/kg) completely blocked the retardant effects of L-PIA on acquisition, although the phosphodiesterase inhibitor rolipram (3.0 mumol/kg) did not. In previously trained animals, L-PIA (5 mumol/kg) also increased the intensity threshold of a tone-conditioned stimulus for eliciting conditioned responses by more than 10 db. Theophylline (200 mumol/kg) and caffeine (300 mumol/kg) had no effect on the intensity threshold of the tone-conditioned stimulus but completely antagonized the effects of L-PIA. It was suggested that the depressant effects of the adenosine analog L-PIA on both the acquisition of conditioned responses and on the ability of a conditioned stimulus to elicit conditioned responses as soon as learning had occurred were mediated by adenosine receptors.
本研究考察了咖啡因、茶碱和咯利普兰对家兔条件反应习得的影响，以及它们拮抗腺苷类似物N6-（L-苯异丙基）腺苷（L-PIA）对习得的抑制作用的能力。通过将800毫秒的音调与光条件刺激的终止与100毫秒的眼部外眦外侧皮肤电击非条件刺激的开始配对，实现瞬膜伸展的巴甫洛夫条件反射。L-PIA（5微摩尔/千克）延缓了对音调与光条件刺激的条件反应的习得，尽管茶碱（50-200微摩尔/千克）、咖啡因（3-100微摩尔/千克）和咯利普兰（0.03-3.0微摩尔/千克）没有影响。所使用的最高剂量咖啡因（300微摩尔/千克）在四个实验中的两个实验中使条件反应习得有小但显著的增强。两种腺苷拮抗剂茶碱（200微摩尔/千克）和咖啡因（300微摩尔/千克）完全阻断了L-PIA对习得的抑制作用，尽管磷酸二酯酶抑制剂咯利普兰（3.0微摩尔/千克）没有。在先前训练的动物中，L-PIA（5微摩尔/千克）还使用于引发条件反应的音调条件刺激的强度阈值提高了超过10分贝。茶碱（200微摩尔/千克）和咖啡因（300微摩尔/千克）对音调条件刺激的强度阈值没有影响，但完全拮抗了L-PIA的作用。有人提出，腺苷类似物L-PIA对条件反应习得以及学习一旦发生条件刺激引发条件反应的能力的抑制作用是由腺苷受体介导的。
