Singh J, Desiraju T, Raju T R
Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Physiol Behav. 1997 Mar;61(3):411-8. doi: 10.1016/s0031-9384(96)00452-0.
This study aimed at investigating the effects of modulators of acetylcholine-muscarinic (ACh-M) and GABAA.B-receptors in the lateral hypothalamus and ventral tegmentum on the electrical self-stimulation evoked from these regions. In each Wistar rat, a bipolar electrode and an ipsilateral insulated cannula-cum-electrode were implanted chronically in the right hemisphere. There were two placement combinations: 1. Bipolar electrode in lateral hypothalamus-medial forebrain bundle (LH-MFB) and cannulacum-electrode in ventral tegmental area-substantia nigra (VTA-SN) or 2, bipolar electrode in VTA-SN and cannula-cum-electrode in LH-MFB. The stimulation parameters were kept at a level to obtain 50% of the maximum possible asymptotic intracranial self-stimulation (ICSS) rates (M50) from each site. Carbachol injected into VTA-SN increased the ICSS responding rate of VTA-SN as well as, indirectly, that of LH-MFB, and atropine injections had an opposite effect. Similar injections of these ligands into LH-MFB again had facilitatory and inhibitory effects on its ICSS: however, there was no indirect effect on the ICSS of VTA-SN. Bicuculline injection into VTA-SN had no effect on either its ICSS or that of LH-MFB. On the other hand, bicuculline injected into LH-MFB decreased its ICSS and, indirectly, the ICSS of VTA-SN in a dose-dependent manner. In contrast, intra VTA-SN injections of picrotoxin decreased its ICSS and, indirectly, ICSS of LH-MFB. Similar injections into LH-MFB had no effect on the ICSS of VTA-SN. The results suggest that ICSS of VTA-SN is Ach-M receptor mediated and, also, this mediation influences the ICSS of LH-MFB. On the contrary, changes in ICSS of LH-MFB following Ach-M receptor ligands do not influence the ICSS of VTA-SN. The direct effects of GABA-receptor antagonists have shown disassociation because ICSS of LH-MFB was more sensitive to bicuculline, whereas the ICSS of VTA-SN was more sensitive to picrotoxin. Thus, the cholinergic and GABAergic mechanisms of the self-stimulation of lateral hypothalamus and ventral tegmentum are different.
本研究旨在探讨下丘脑外侧区和腹侧被盖区中乙酰胆碱 - 毒蕈碱（ACh - M）和GABAA.B受体调节剂对这些区域诱发的电自我刺激的影响。在每只Wistar大鼠的右半球慢性植入一个双极电极和一个同侧绝缘套管兼电极。有两种放置组合：1. 双极电极置于下丘脑外侧区 - 内侧前脑束（LH - MFB），套管兼电极置于腹侧被盖区 - 黑质（VTA - SN）；或2. 双极电极置于VTA - SN，套管兼电极置于LH - MFB。刺激参数保持在一个水平，以从每个部位获得最大可能渐近颅内自我刺激（ICSS）率的50%（M50）。注入VTA - SN的卡巴胆碱增加了VTA - SN的ICSS反应率，并且间接增加了LH - MFB的ICSS反应率，而注射阿托品则产生相反的效果。将这些配体类似地注入LH - MFB对其ICSS再次产生促进和抑制作用；然而，对VTA - SN的ICSS没有间接影响。注入VTA - SN的荷包牡丹碱对其ICSS或LH - MFB的ICSS均无影响。另一方面，注入LH - MFB的荷包牡丹碱以剂量依赖性方式降低其ICSS，并间接降低VTA - SN的ICSS。相反，向VTA - SN内注射印防己毒素降低其ICSS，并间接降低LH - MFB的ICSS。向LH - MFB进行类似注射对VTA - SN的ICSS没有影响。结果表明，VTA - SN的ICSS是由ACh - M受体介导的，并且这种介导影响LH - MFB的ICSS。相反，ACh - M受体配体作用后LH - MFB的ICSS变化不影响VTA - SN的ICSS。GABA受体拮抗剂的直接作用表现出分离现象，因为LH - MFB的ICSS对荷包牡丹碱更敏感，而VTA - SN的ICSS对印防己毒素更敏感。因此，下丘脑外侧区和腹侧被盖区自我刺激的胆碱能和GABA能机制是不同的。
