Division of Systems Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
Robarts Research Institute, University of Western Ontario, 1151 Richmond Street North, London, ON, N6A 5B7, Canada.
Sci Rep. 2019 Mar 26;9(1):5206. doi: 10.1038/s41598-019-41568-5.
In opioid addiction, cues and contexts associated with drug reward can be powerful triggers for drug craving and relapse. The synapses linking ventral hippocampal outputs to medium spiny neurons of the accumbens may be key sites for the formation and storage of associations between place or context and reward, both drug-related and natural. To assess this, we implanted rats with electrodes in the accumbens shell to record synaptic potentials evoked by electrical stimulation of the ventral hippocampus, as well as continuous local-field-potential activity. Rats then underwent morphine-induced (10 mg/kg) conditioned-place-preference training, followed by extinction. Morphine caused an acute increase in the slope and amplitude of accumbens evoked responses, but no long-term changes were evident after conditioning or extinction of the place preference, suggesting that the formation of this type of memory does not lead to a net change in synaptic strength in the ventral hippocampal output to the accumbens. However, analysis of the local field potential revealed a marked sensitization of theta- and high-gamma-frequency activity with repeated morphine administration. This phenomenon may be linked to the behavioral changes-such as psychomotor sensitization and the development of drug craving-that are associated with chronic use of addictive drugs.
在阿片成瘾中，与药物奖赏相关的线索和情境可能是药物渴望和复发的强大触发因素。腹侧海马输出到伏隔核中间神经元的突触可能是形成和储存位置或情境与奖赏之间关联的关键部位，包括与药物相关的和自然的奖赏。为了评估这一点，我们将电极植入大鼠的伏隔核壳中，以记录腹侧海马电刺激诱发的突触电位以及连续的局部场电位活动。然后，大鼠接受吗啡诱导的（10mg/kg）条件性位置偏好训练，随后进行消退。吗啡引起伏隔核诱发反应的斜率和幅度急性增加，但在条件性位置偏好的形成或消退后没有明显的长期变化，这表明这种类型的记忆的形成不会导致伏隔核输出到伏隔核的突触强度发生净变化。然而，局部场电位分析显示，反复给予吗啡会导致θ和高γ频率活动明显敏化。这种现象可能与行为变化有关，例如运动敏化和药物渴望的发展，这些变化与成瘾性药物的慢性使用有关。
