Olmstead M C, Munn E M, Franklin K B, Wise R A
Department of Psychology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
J Neurosci. 1998 Jul 1;18(13):5035-44. doi: 10.1523/JNEUROSCI.18-13-05035.1998.
The pedunculopontine tegmental nucleus (PPTg) is believed to play important roles in reward and learning. We examined the effect of PPTg lesions (0.5 microl of 0.1 M NMDA injected bilaterally over 10 min) on the learning of an operant response for opiate reward. In 14 adult male Long-Evans rats, bilateral lesions of the PPTg disrupted the acquisition of responding for intravenous heroin (0.1 mg/kg infused at a rate of 0.25 ml/28 sec) on a fixed ratio-1 (FR-1) schedule of reinforcement. The 12 remaining lesioned animals increased their heroin intake over the acquisition sessions but did not reach the response levels of sham-lesioned animals on the 15th and final session. The sham- and PPTg-lesioned animals that learned the FR-1 task exhibited similar patterns of responding during extinction and reacquisition sessions. When tested on a progressive ratio (PR) schedule of reinforcement, however, PPTg-lesioned animals had lower break points than sham-lesioned animals. Asymmetric lesions, which destroyed the majority of the nucleus in one hemisphere only, did not produce any behavioral deficits. Rats that were lesioned after training also did not show deficits in responding under either FR or PR schedules. These findings suggest that PPTg lesions reduce the rewarding effect of opiates but do not disrupt the ability either to learn an operant response or the response requirements of a PR schedule.
脚桥被盖核(PPTg)被认为在奖赏和学习中发挥重要作用。我们研究了脚桥被盖核损伤(在10分钟内双侧注射0.5微升0.1M的N-甲基-D-天冬氨酸)对阿片类奖赏操作性反应学习的影响。在14只成年雄性Long-Evans大鼠中,脚桥被盖核的双侧损伤破坏了在固定比率-1(FR-1)强化程序下对静脉注射海洛因(以0.25毫升/28秒的速度注入0.1毫克/千克)做出反应的习得。其余12只损伤动物在习得过程中增加了海洛因摄入量,但在第15次也是最后一次实验中未达到假损伤动物的反应水平。学会FR-1任务的假损伤和脚桥被盖核损伤动物在消退和重新习得实验期间表现出相似的反应模式。然而,在渐进比率(PR)强化程序下进行测试时,脚桥被盖核损伤动物的断点低于假损伤动物。仅破坏一个半球中大部分核的不对称损伤未产生任何行为缺陷。训练后接受损伤的大鼠在FR或PR程序下的反应也未显示出缺陷。这些发现表明,脚桥被盖核损伤会降低阿片类药物的奖赏作用,但不会破坏学习操作性反应的能力或PR程序的反应要求。