Sexual motivation exerts a strong influence on human behavior and is a particularly important area in human psychosocial development. Sexual interest and enjoyment are domains that are often adversely affected by psychiatric disorders, especially mood disorders. Primary disorders of sexual desire and function are also common. Research into the basic neurobiology of sexual motivation may provide insight into the pathophysiology of aberrant sexual desire and behavior as well as lead to more effective treatments for these disorders. The current proposal is built upon three recent observations. First, in low dose estrogen (E)-primed rats given a dose of progesterone (P) that stimulates sexual behavior, infusion of oxytocin (OT) antagonist into the medial preoptic area (MPOA), but not infusion into the ventromedial nucleus (VMN), blocked receptivity and increased rejection behaviors and audible vocalizations when males attempted to mount. OT antagonist was effective when given just before P treatment but not when given prior to behavioral testing 4 hours later. Second, infusion of a selective vasopressor (V1) antagonist into the MPOA potently stimulated sexual receptivity in low dose E-primed rats, suggesting that arginine vasopressin (AVP) may exert a chronic inhibitory influence on female sexual behavior in this brain site. Third, high dose E treatment that stimulates female sexual behavior significantly increased OT binding affinity (Kd) in the MPOA but not in the medial basal hypothalamus (containing the VMN) or other brain sites.
The Specific Aims of the proposed project are 1) to clarify which components of female sexual behavior are specifically regulated by OT receptors, 2) to determine whether there is a """"""""critical period"""""""" after P treatment in low dose E-primed rats during which OT receptor activation in the MPOA is necessary for the subsequent rise in female sexual behavior; 3) to examine the role of OT in the MPOA and VMN in female rats' sexual behavior occurring after high dose E treatment, on the evening of proestrus, or after parturition; 4) to further investigate the behavioral pharmacology of AVP and V1 antagonist effects on female sexual behavior in the MPOA; 5) to study the effects of ovarian steroids on sensitivity to OT or V1 antagonist stimulation of female sexual behavior; 6) to examine the effects of ovarian steroid treatments that stimulate female sexual behavior (low dose E+P, high dose E) on OT and V1 binding and OT and AVP content in the MPOA and VMN.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH056157-01A1
Application #
2034940
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Project Start
1997-09-01
Project End
2001-04-30
Budget Start
1997-09-01
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599