Effects of Microinjections of Cholecystokinin and Neurotensin into Lateral Hypothalamus and Ventral Mesencephalon on Intracranial Self-Stimulation

Abstract

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-Tyr 11]NT 1–13 or [DTrp 11] 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 μg/0.5 μl and 0.25 μg/0.5 μl) 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 (NT 1) receptor agonist [DTyr 11]NT 1–13 and the NT 1 receptor antagonist [D-Trp 11]NT 1–13 at doses of 5 μg/0.5 μl and 10 μg/0.5 μl decreased VTA-SN ICSS. NT 1 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-Trp 11]NT 1–13 on VTA-SN ICSS and restored basal preinjection rates of responding. These results suggest that CCK A and NT 1 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.