Effects of arginine-vasopressin fragment 4-9 on rodent cholinergic systems

Arginine-vasopressin fragment 4-9 (AVP(4-9)) has been demonstrated in anima l studies to facilitate learning and memory. To clarify the mechanisms of t his facilitation, we focused on the effects of AVP(4-9) on rodent cholinerg ic systems. AVP(4-9) (0.1 mu M) enhanced the basal and the high-potassium-e voked acetylcholine (ACh) release from rat hippocampal slices (122.4 and 12 0.0% of control, respectively) in the presence of 1.3 mM calcium (physiolog ical level) at 60 min after the incubation at 37 degrees C. The AVP(4-9)-st imulated basal ACh release was inhibited by a V-1-selective antagonist ([(b eta-mercapto-beta,beta-cyclopentamethylene propionic acid)(1), O-methyl-Tyr (2), Arg(8)] vasopressin), but not by a V-2-selective antagonist ([adamanta neacetyl(1), O-ethyl-D-Tyr(2), Val(4), aminobutyryl(6), Arg(8,9)]-vasopress in). In addition, AVP(4-9) did not affect the basal ACh release under the c alcium-free condition at 37 degrees C or in the presence of 1.3 mM calcium at 4 degrees C. However, AVP(4-9) facilitated the passive-avoidance respons e of scopolamine (a cholinergic blocker)-induced memory-deficient mice. The se findings demonstrate that AVP(4-9) stimulates ACh release via mediation by V-1-like vasopressin receptors, and shows dependence on calcium ion and temperature. The results also suggest that the mechanism of the facilitativ e effects of AVP(4-9) on learning and memory consist of the observed stimul ation of cholinergic systems and other parallel pathways that would not be inhibited by cholinergic blocking. (C) 1999 Elsevier Science Inc.