SUT-8701, a Cholecystokinin Analog, Prevents the Cholinergic Degeneration in the Rat Cerebral Cortex Following Basal Forebrain Lesioning

Abstract

SUT-8701 is a cholecystokinin octapeptide (CCK8)analog and a more lipophilic peptide than CCK8. We previously demonstrated that intra-ventricularly administered CCK8 protected against the degeneration of the cholinergic neurons in the cortex of the nucleus basalis magnocellularis (nbm)-lesioned rat. We determined whether SUT-8701 and CCK8 have the ability to protect against cholinergic degeneration in the cerebral cortex of nbm-lesioned rats. Systemically administered SUT-8701 (0.1-1 μg/day/animal, s.c.)preserved choline acetyltransferase activity and K⁺-evoked acetylcholine release in nbm-lesioned rats. SUT-8701 was more potent than CCK8. However, SUT-8701 was much less potent than CCK8 in satiety action. The affinity of SUT-8701 to the cholecystokinin (CCK)receptors assessed by using [¹²⁵I]-CCK8 was almost the same as that of CCK8 in the mouse cerebral cortex, but was 107 times less than that of CCK8 in guinea pig pancreas. These results suggest that SUT-8701 may be effective in slowing down the degenerative processes in Alzheimer''s disease by preserving the integrity of cholinergic neurons in the nucleus basalis.