Homberg J R, Wardeh G, Raasø H S, Schoffelmeer A N M, De Vries T J
Research Institute Neurosciences Vrije Universiteit, Drug Abuse Program, Department of Medical Pharmacology, VU Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Neuroscience. 2003;121(4):829-36. doi: 10.1016/j.neuroscience.2003.07.001.
Previously, we demonstrated that stress-induced self-grooming behaviour in rats predicted an enhanced motivation to self-administer cocaine as determined under a progressive ratio schedule of reinforcement. The enhanced motivation of high grooming (HG) rats was associated with a reduced reactivity of dopaminergic neurons in the medial prefrontal cortex and amygdala, but not nucleus accumbens. In the present study, we studied the effect of cocaine and saline self-administration on these pre-existing differences in neurochemical profile by determining the electrically evoked release of [3H]dopamine and [14C]acetylcholine from superfused slices of the nucleus accumbens shell and core, medial prefrontal cortex and amygdala of HG and low grooming (LG) rats. Although HG and LG rats did not differ in acquisition of cocaine and saline self-administration, both conditions induced substantially different neuroadaptations in these rats. Differences in depolarisation-induced dopamine and acetylcholine release were maintained in the medial prefrontal cortex, emerged in the nucleus accumbens and dissipated in the amygdala. These results indicate that altered reactivity of mesocorticolimbic dopaminergic and cholinergic neurons due to exposure to cocaine and environmental stimuli (saline) is dependent on pre-existing neurochemical differences and displays region-specificity. These pre-existing differences and the cocaine- and environmental-induced neuroadaptations seem to act in concert to produce an enhanced motivational state to self-administer cocaine.
此前，我们证明，大鼠应激诱导的自我梳理行为预示着在渐进性比率强化程序下自我给药可卡因的动机增强。高梳理（HG）大鼠动机增强与内侧前额叶皮质和杏仁核中多巴胺能神经元反应性降低有关，但伏隔核中多巴胺能神经元反应性未降低。在本研究中，我们通过测定HG和低梳理（LG）大鼠伏隔核壳部和核心、内侧前额叶皮质和杏仁核的灌流切片中电诱发的[3H]多巴胺和[14C]乙酰胆碱释放，研究了可卡因和生理盐水自我给药对这些预先存在的神经化学特征差异的影响。尽管HG和LG大鼠在可卡因和生理盐水自我给药的习得方面没有差异，但这两种情况在这些大鼠中诱导了截然不同的神经适应性变化。内侧前额叶皮质中去极化诱导的多巴胺和乙酰胆碱释放差异得以维持，伏隔核中出现差异，杏仁核中的差异则消失。这些结果表明，由于接触可卡因和环境刺激（生理盐水）导致的中脑边缘多巴胺能和胆碱能神经元反应性改变取决于预先存在的神经化学差异，并具有区域特异性。这些预先存在的差异以及可卡因和环境诱导的神经适应性变化似乎共同作用，产生增强的自我给药可卡因的动机状态。
