Itzhak Yossef, Perez-Lanza Daniel, Liddie Shervin
Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
IUBMB Life. 2014 Aug;66(8):559-71. doi: 10.1002/iub.1310. Epub 2014 Sep 5.
Certain maladaptive behaviors are thought to be acquired through classical Pavlovian conditioning. Exaggerated fear response, which can develop through Pavlovian conditioning, is associated with acquired anxiety disorders such as post-traumatic stress disorders (PTSDs). Inflated reward-seeking behavior, which develops through Pavlovian conditioning, underlies some types of addictive behavior (e.g., addiction to drugs, food, and gambling). These maladaptive behaviors are dependent on associative learning and the development of long-term memory (LTM). In animal models, an aversive reinforcer (fear conditioning) encodes an aversive contextual and cued LTM. On the other hand, an appetitive reinforcer results in conditioned place preference (CPP) that encodes an appetitive contextual LTM. The literature on weak and strong associative learning pertaining to the development of aversive and appetitive LTM is relatively scarce; thus, this review is particularly focused on the strength of associative learning. The strength of associative learning is dependent on the valence of the reinforcer and the salience of the conditioned stimulus that ultimately sways the strength of the memory trace. Our studies suggest that labile (weak) aversive and appetitive LTM may share similar signaling pathways, whereas stable (strong) aversive and appetitive LTM is mediated through different pathways. In addition, we provide some evidence suggesting that extinction of aversive fear memory and appetitive drug memory is likely to be mediated through different signaling molecules. We put forward the importance of studies aimed to investigate the molecular mechanisms underlying the development of weak and strong memories (aversive and appetitive), which would ultimately help in the development of targeted pharmacotherapies for the management of maladaptive behaviors that arise from classical Pavlovian conditioning.
某些适应不良行为被认为是通过经典的巴甫洛夫条件反射习得的。通过巴甫洛夫条件反射可能产生的过度恐惧反应与创伤后应激障碍(PTSD)等后天焦虑症有关。通过巴甫洛夫条件反射形成的过度寻求奖励行为是某些成瘾行为(如药物成瘾、食物成瘾和赌博成瘾)的基础。这些适应不良行为依赖于联想学习和长期记忆(LTM)的形成。在动物模型中,厌恶强化物(恐惧条件反射)编码厌恶情境和线索性长期记忆。另一方面,奖赏性强化物会导致条件性位置偏爱(CPP),它编码奖赏性情境长期记忆。关于与厌恶和奖赏性长期记忆形成相关的弱联想学习和强联想学习的文献相对较少;因此,本综述特别关注联想学习的强度。联想学习的强度取决于强化物的效价和条件刺激的显著性,最终影响记忆痕迹的强度。我们的研究表明,不稳定(弱)的厌恶和奖赏性长期记忆可能共享相似的信号通路,而稳定(强)的厌恶和奖赏性长期记忆则通过不同的通路介导。此外,我们提供了一些证据表明,厌恶恐惧记忆和奖赏性药物记忆的消退可能通过不同的信号分子介导。我们提出了旨在研究弱记忆和强记忆(厌恶和奖赏性)形成背后分子机制的研究的重要性,这最终将有助于开发针对性的药物疗法,以管理由经典巴甫洛夫条件反射引起的适应不良行为。