Dopamine (DA) is released in the medial preoptic area (MPOA) of male rats in the presence of a receptive female, and it facilitates their copulation. Precopulatory DA release is highly predictive of copulatory ability. Testosterone (T) increases basal and female-stimulated DA release by up-regulating nitric oxide synthase (NOS), which produces nitric oxide (NO), which in turn increases DA release. We will now determine the hormonal and cellular factors that regulate DA release in the MPOA and will also determine the consequences of MPOA DA release on amino acid neurotransmitters.
Aim 1 will determine whether T metabolites applied directly to the MPOA can maintain copulation, DA release, NOS immunoreactivity and DA receptors. We will also test whether androgen receptor-containing neurons in the MPOA are also immunoreactive for subtypes of DA receptors and whether castration affects those receptors.
Aim 2 will determine the cellular factors that regulate the release of dopamine in the MPOA and the immediate consequences of DA release. Interactions with cGMP, glutamate, and GABA will be studied with both microdialysis and immunocytochemistry.
Aim 3 will test mechanism(s) by which sexual experience may facilitate copulation. We will test whether basal or female-stimulated MPOA DA levels are higher in experienced than in naive males and whether injection of an NMDA antagonist into the MPOA prevents the facilitative effects of repeated exposures to a female.
Aim 4 will determine the nature and functional significance of a major input to the MPOA. Lesions of the medial amygdala (MeA) blocked the MPOA DA response to a female and impaired copulation. Microinjection of a DA agonist into the MPOA restored copulatory ability in males with MeA lesions. We will now test whether electrical stimulation of the MeA increases DA, glutamate, and/or GABA release in the MPOA and whether axons from the MeA end near MPOA neurons that are immunoreactive for glutamate or GABA receptors or NOS. Two major clinical treatments for erectile disorder either prolong NO's peripheral and central effects or stimulate DA receptors; however, both have undesirable side effects. This research may lead to better treatments for sexual dysfunctions with fewer side effects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
7R01MH040826-18
Application #
6999585
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Quinn, Kevin J
Project Start
1988-08-01
Project End
2006-04-30
Budget Start
2005-03-22
Budget End
2005-04-30
Support Year
18
Fiscal Year
2004
Total Cost
$181,915
Indirect Cost
Name
Florida State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
790877419
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
McHenry, Jenna A; Robison, Christopher L; Bell, Genevieve A et al. (2016) The role of ?fosB in the medial preoptic area: Differential effects of mating and cocaine history. Behav Neurosci 130:469-78
McHenry, Jenna; Carrier, Nicole; Hull, Elaine et al. (2014) Sex differences in anxiety and depression: role of testosterone. Front Neuroendocrinol 35:42-57
Gil, Mario; Bhatt, Renu; Picotte, Katie B et al. (2013) Sexual experience increases oxytocin receptor gene expression and protein in the medial preoptic area of the male rat. Psychoneuroendocrinology 38:1688-97
McHenry, Jenna A; Bell, Genevieve A; Parrish, Bradley P et al. (2012) Dopamine D1 receptors and phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein-32 in the medial preoptic area are involved in experience-induced enhancement of male sexual behavior in rats. Behav Neurosci 126:523-9
Vigdorchik, Anna V; Parrish, Bradley P; Lagoda, Gwen A et al. (2012) An NMDA antagonist in the MPOA impairs copulation and stimulus sensitization in male rats. Behav Neurosci 126:186-95
Hull, Elaine M (2011) Sex, drugs and gluttony: how the brain controls motivated behaviors. Physiol Behav 104:173-7
Gil, Mario; Bhatt, Renu; Picotte, Katie B et al. (2011) Oxytocin in the medial preoptic area facilitates male sexual behavior in the rat. Horm Behav 59:435-43
Hull, Elaine M; Dominguez, Juan M (2007) Sexual behavior in male rodents. Horm Behav 52:45-55
Muschamp, John W; Dominguez, Juan M; Sato, Satoru M et al. (2007) A role for hypocretin (orexin) in male sexual behavior. J Neurosci 27:2837-45
Muschamp, John W; Hull, Elaine M (2007) Melanin concentrating hormone and estrogen receptor-alpha are coexstensive but not coexpressed in cells of male rat hypothalamus. Neurosci Lett 427:123-6

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