Arginine vasopressin (AVP), a posterior pituitary peptide hormone, has been shown to have several non-renal actions including the maintenance of learned avoidance behaviors, and recently, in humans, improvement in cognitive functioning. Preliminary research in our laboratory has confirmed some of these behavioral effects in animals and begun an attempt to examine the behavioral and physiological basis of this effect. The present proposal for research will focus on determining the physiological mechanism by which AVP produces its behavioral effects. Behavioral experiments will concentrate on examining the effects of AVP in rats on two tests of """"""""memory"""""""", an active avoidance task and a spatial forgetting test, and one test of """"""""emotionality"""""""" the Geller-Seifter conflict test. These tests have been chosen to control for the nature of the unconditioned stimulus (aversive vs. appetitive), motor debilitating effects, and motivational effects of AVP itself. The importance of peripheral mechanisms related to the classical endocrinological effects of AVP will be determined by using these behavioral tests and analogs of AVP, some of which are specific antagonists of certain endocrinological effects. In addition, an attempt will be made to identify the distribution and site of action of exogenously applied AVP using radioimmunoassay and intracerebral injections. This basic research directed at understanding the mechanism of action of the effects of vasopressin on behavior has important implications for the possible therapeutic use of vasopressin in cognitive disorders associated with aging, and other biologically based learning disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020912-03
Application #
3401571
Study Section
Biopsychology Study Section (BPO)
Project Start
1983-12-01
Project End
1986-07-31
Budget Start
1985-06-01
Budget End
1986-07-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037
Koob, G F; Lebrun, C; Bluthe, R M et al. (1989) Role of neuropeptides in learning versus performance: focus on vasopressin. Brain Res Bull 23:359-64
Lebrun, C; Le Moal, M; Dantzer, R et al. (1987) Hypertonic saline mimics the effects of vasopressin on inhibitory avoidance in the rat. Behav Neural Biol 47:130-7
Koob, G F; Dantzer, R; Bluthe, R M et al. (1986) Central injections of arginine vasopressin prolong extinction of active avoidance. Peptides 7:213-8
Lebrun, C; Le Moal, M; Koob, G F et al. (1985) Vasopressin pressor antagonist injected centrally reverses behavioral effects of peripheral injection of vasopressin, but only at doses that reverse increase in blood pressure. Regul Pept 11:173-81
Koob, G F; Lebrun, C; Martinez Jr, J L et al. (1985) Arginine vasopressin, stress, and memory. Ann N Y Acad Sci 444:194-202