Singh J, Desiraju T, Raju T R
Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Pharmacol Biochem Behav. 1997 Dec;58(4):893-8. doi: 10.1016/s0091-3057(97)00040-3.
Changes in intracranial self-stimulation (ICSS) evoked from ventral tegmental area-substantia nigra (VTA-SN) and lateral hypothalamus-medial forebrain bundle (LH-MFB) before and after microinjections of sulfated cholecystokinin octapeptide (CCK-8S) and unsulfated cholecystokinin (CCK-8US), neurotensin tridecapeptide ([D-Tyr11]NT(1-13) or [DTrp11]NT(1-13)) into either VTA-SN or LH-MFB were assessed. The current intensity was fixed at a level to obtain 60-70% of the maximal asymptotic rate. CCK-8S (0.10 microg/0.5 microl and 0.25 microg/0.5 microl) into VTA-SN resulted in dose-dependent decreases in VTA-SN ICSS of 38-42% and 78-92%, respectively, without affecting the ICSS of LH-MFB. Similar doses of CCK-8S injected into LH-MFB changed neither LH-MFB ICSS nor VTA-SN ICSS. CCK-8Us injected into VTA-SN or LH-MFB had no effect on ICSS in either site. Intra-VTA-SN injections of the neurotensin-1 (NT1) receptor agonist [DTyr11]NT(1-13) and the NT1 receptor antagonist [D-Trp11]NT(1-13) at doses of 5 microg/0.5 microl and 10 microg/0.5 microl decreased VTA-SN ICSS. NT1 receptor agonist and antagonist injections did not alter LH-MFB ICSS in any significant manner. Similar injections of these peptides into LH-MFB did not change the responding rates for LH-MFB ICSS or VTA-SN ICSS. Increasing the current intensity reversed the inhibitory effect of CCK-8S and [D-Trp11]NT(1-13) on VTA-SN ICSS and restored basal preinjection rates of responding. These results suggest that CCK(A) and NT1 receptor mechanisms in the ventral tegmentum in association with dopamine neurotransmission may be important in mediating the rewarding effects of VTA-SN ICSS but not LH-MFB ICSS.
评估了向腹侧被盖区-黑质（VTA-SN）和外侧下丘脑-内侧前脑束（LH-MFB）微量注射硫酸化八肽胆囊收缩素（CCK-8S）和非硫酸化胆囊收缩素（CCK-8US）、神经降压素十三肽（[D-Tyr11]NT(1-13) 或 [DTrp11]NT(1-13)）前后，从VTA-SN和LH-MFB诱发的颅内自我刺激（ICSS）的变化。电流强度固定在一个能获得最大渐近速率60 - 70%的水平。向VTA-SN注射CCK-8S（0.10微克/0.5微升和0.25微克/0.5微升）分别导致VTA-SN的ICSS剂量依赖性降低38 - 42%和78 - 92%，而不影响LH-MFB的ICSS。向LH-MFB注射相似剂量的CCK-8S既不改变LH-MFB的ICSS也不改变VTA-SN的ICSS。向VTA-SN或LH-MFB注射CCK-8US对任一部位的ICSS均无影响。向VTA-SN内注射剂量为5微克/0.5微升和10微克/0.5微升的神经降压素-1（NT1）受体激动剂[DTyr1]NT(1-13)和NT1受体拮抗剂[D-Trp11]NT(1-13)降低了VTA-SN的ICSS。NT1受体激动剂和拮抗剂注射未以任何显著方式改变LH-MFB的ICSS。向LH-MFB进行类似的肽注射未改变LH-MFB ICSS或VTA-SN ICSS的反应率。增加电流强度可逆转CCK-8S和[D-Trp11]NT(1-13)对VTA-SN ICSS的抑制作用，并恢复注射前的基础反应率。这些结果表明，腹侧被盖区中与多巴胺神经传递相关的CCK(A)和NT1受体机制可能在介导VTA-SN的ICSS奖赏效应中起重要作用，但对LH-MFB的ICSS不起作用。
