Zacharko R M, Maddeaux C, Hebb A L, Mendella P D, Marsh N J
Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Brain Res Bull. 1998 Oct;47(3):237-48. doi: 10.1016/s0361-9230(98)00082-3.
D-Ala2-Met5-enkephalinamide (DALA) (1.0 microg/microl) was administered intraventricularly to mice responding for electrical stimulation from the dorsal or ventral aspects of the VTA immediately prior to footshock (Experiment 1). Predictably, footshock reduced self-stimulation from the dorsal but not the ventral VTA immediately, 24, and 168 h following the stressor. Intraventricular DALA administration effected a partial attenuation of stressor-induced self-stimulation reductions from the dorsal VTA immediately and 24 h poststressor. Deficits appeared among DALA-Shocked mice responding for brain stimulation from the ventral VTA during comparable test intervals. The long-term depressant influence of footshock on self-stimulation from the dorsal VTA was abolished among DALA-treated mice and DALA-associated reductions in self-stimulation from the ventral A10 region among stressed mice were not evident 1 week later. Administration of D-Ala2, N-Me-Phe4, Gly-Ol5-enkephalin (DAGO) (0.01 microg/microl) or D-Pen2, D-Pen5-enkephalin (DPDPE) (1.0 microg/microl) intraventricularly prior to footshock effected an immediate and a delayed antagonism, respectively, of the stressor on self-stimulation from the dorsal VTA, which persisted for 1 week. Prophylactic administration of 0.001 microg/microl DAGO or 0.01 microg/microl DPDPE prior to the stressor failed to influence self-stimulation from the ventral VTA (Experiment 2). Administration of 0.01 microg/microl DAGO or 1.0 microg/microl DPDPE among mice responding for brain stimulation from the dorsal VTA following footshock produced a weak therapeutic effect immediately poststressor, but effected protracted amelioration of footshock-induced reductions of self-stimulation from the dorsal VTA (Experiment 3). Taken together, mu, delta, and mu-delta activation influenced self-stimulation differentially from the dorsal and ventral VTA according to the temporal order of opioid peptide challenge relative to stressor imposition. These data are discussed with respect to stressors, motivational alterations, and the putative modulating influence of endogenous enkephalin activity in subareas of the VTA.
在电击足底（实验1）之前，向因接受来自腹侧被盖区背侧或腹侧的电刺激而做出反应的小鼠脑室内注射D - 丙氨酸2 - 甲硫氨酸5 - 脑啡肽酰胺（DALA）（1.0微克/微升）。不出所料，电击足底后立即、24小时和168小时，电击足底使来自背侧而非腹侧腹侧被盖区的自我刺激立即减少。脑室内注射DALA使应激源诱导的背侧腹侧被盖区自我刺激减少在应激源施加后立即和24小时部分减弱。在可比的测试间隔期间，对来自腹侧腹侧被盖区的脑刺激做出反应的DALA - 电击小鼠出现了缺陷。在接受DALA治疗的小鼠中，电击足底对背侧腹侧被盖区自我刺激的长期抑制作用被消除，并且在应激小鼠中，1周后与DALA相关的腹侧A10区自我刺激减少不明显。在电击足底之前脑室内注射D - 丙氨酸2，N - 甲基 - 苯丙氨酸4，甘氨酸 - 醇5 - 脑啡肽（DAGO）（0.01微克/微升）或D - 青霉胺2，D - 青霉胺5 - 脑啡肽（DPDPE）（1.0微克/微升）分别对应激源对背侧腹侧被盖区自我刺激产生即时和延迟的拮抗作用，这种作用持续1周。在应激源之前预防性注射0.001微克/微升DAGO或0.01微克/微升DPDPE未能影响来自腹侧腹侧被盖区的自我刺激（实验2）。在电击足底后对来自背侧腹侧被盖区的脑刺激做出反应的小鼠中注射0.01微克/微升DAGO或1.0微克/微升DPDPE在应激源后立即产生微弱的治疗效果，但对应激源诱导的背侧腹侧被盖区自我刺激减少产生持久的改善作用（实验3）。综上所述，根据阿片肽激发相对于应激源施加的时间顺序，μ、δ和μ - δ激活对来自背侧和腹侧腹侧被盖区的自我刺激有不同影响。将结合应激源、动机改变以及腹侧被盖区各亚区内内源性脑啡肽活性的假定调节作用来讨论这些数据。
