Project Details
Description
DESCRIPTION
Sexual dysfunction in women is primarily characterized by low levels of sexual arousal and
desire. Because no effective treatments exist for disorders of sexual desire in women, the FDA
was pressured to fast-track approval for the drug Addyi despite the absence of clinical evidence
that the drug provided any therapeutic benefit. Underlying the inability to construct a rational
approach to developing therapeutics for disorders of sexual desire in women is the lack of
research on the mechanistic basis for female sexual desire in pre-clinical models. We have
developed a Syrian hamster model of sexual desire that captures several essential elements
needed to translate the findings to women. We developed a procedure to evaluate the
rewarding properties of female sexual behavior, an element reported to be lacking in women
with low sexual desire. Women with low sexual desire also do not initiate sexual contacts with
their spouse or partner. In this regard we discovered an experimental approach to test the
female hamster's willingness to initiate sexual contacts with a male. Based on these hamster
studies we demonstrated that the rewarding consequences of sexual interactions with a male
feed forward to increase the female's sexual contacts. We further identified the mesolimbic
dopamine system, and prefrontal glutamatergic afferents, centered on the nucleus accumbens,
as a critical neural node mediating the rewarding effects of sexual behavior in females. The
research in this proposal takes three specific approaches to establish a programmatic
understanding of the neurobiology of female sexual desire. In the first aim we will use inhibitory
DREADDs to determine the relative contribution of dopamine and glutamate afferents to the
nucleus accumbens to the development of sexual reward and initiation of sexual interactions
with the male in our hamster model. We will also examine the contributions of these afferents to
changes in dendritic spine morphology consequent to female sexual experience. The second
aim takes a discovery approach to examining three possible intracellular signaling pathways
mediating the effects of sexual experience on behavioral and morphological plasticity. The last
aim will pharmacologically manipulate the individual signaling pathways to identify which of
these pathways are potential molecular targets for therapeutic development to treat problems of
sexual desire in women. Collectively this research will take a systematic approach to developing
a neurobiology of female sexual desire with an eye to the rational development of effective
therapies.
Status | Finished |
---|---|
Effective start/end date | 3/15/19 → 2/29/24 |
Funding
- National Institute of Child Health and Human Development: $327,250.00
- National Institute of Child Health and Human Development: $56,105.00
- National Institute of Child Health and Human Development: $98,199.00
- Eunice Kennedy Shriver National Institute of Child Health and Human Development: $320,705.00
- National Institute of Child Health and Human Development: $327,250.00
- National Institute of Child Health and Human Development: $320,705.00
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