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Illustrating the Circuits of Sexual Desire

Stephen M. Stahl, MD, PhD

Published: September 15, 2010

Illustrating the Circuits of Sexual Desire

Issue: Malfunctioning reward pathways may mediate the reduction of sexual desire caused by depression, sexual disorders, endocrine disorders, hormones, and various psychotropic drugs. Effective treatments for reduced libido target these circuits by enhancing dopamine, reducing serotonin, or both.

Take-Home Points

  • Reward pathways connect the prefrontal cortex with many key brain regions, including neurotransmitter centers, limbic emotional areas, and the hypothalamus.
  • In these circuits, some neurotransmitters, such as dopamine, norepinephrine, oxytocin, and melanocortins, cause sexual excitation whereas other neurotransmitters, such as serotonin, opioids, and endocannabinoids, inhibit sexual excitation in these same circuits.
  • Drugs, hormones, and disorders that disrupt sexual desire may either reduce the neurotransmitters of sexual excitation or enhance the neurotransmitters of sexual inhibition.
  • Potential treatments for reduced sexual desire are those that promote dopamine, oxytocin, or melanocortins or block serotonin in reward pathways.
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Figure 2

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1. Stahl SM. Circuits of sexual desire in hypoactive sexual desire disorder. J Clin Psychiatry. 2010;71(5):518-519. PubMed doi:10.4088/JCP.10bs06115whi

2. Pfaus JG. Pathways of sexual desire. J Sex Med. 2009;6(6):1506-1533. PubMed doi:10.1111/j.1743-6109.2009.01309.x

3. Arnow BA, Millheiser L, Garrett A, et al. Women with hypoactive sexual desire disorder compared to normal females: a functional magnetic resonance imaging study. Neuroscience. 2009;158(2):484-502. PubMed doi:10.1016/j.neuroscience.2008.09.044

4. Holstege G, Willemsen A, Beers C, et al. Differences in brain activity in premenopausal women with hypoactive sexual desire disorder (HSDD) compared to women without sexual dysfunction. Abstracts of the 12th Congress of the European Society for Sexual Medicine (ESSM), November 15-18, 2009; Lyon, France. PS-02-002.

5. Stahl SM. Targeting circuits of sexual desire as a treatment strategy for HSDD (hypoactive sexual desire disorder). J Clin Psychiatry. 2010;71(7):821-822. doi:10.4088/JCP.10bs06117blu

6. Bortolozzi A, Dí­az-Mataix L, Scorza MC, et al. The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity.
J Neurochem. 2005;95(6):1597-1607. PubMed doi:10.1111/j.1471-4159.2005.03485.x

7. Invernizzi RW, Sacchetti G, Parini S, et al. Flibanserin, a potential antidepressant drug, lowers 5-HT and raises dopamine and noradrenaline in the rat prefrontal cortex dialysate: role of 5-HT(1A) receptors. Br J Pharmacol. 2003;139(7):1281-1288. PubMed doi:10.1038/sj.bjp.0705341

8. Jolly E, Clayton A, Thorp J, et al. Efficacy of flibanserin 100 mg qhs as a potential treatment for hypoactive sexual desire disorder in premenopausal women. Abstracts of the 12th Congress of the European Society for Sexual Medicine (ESSM). November 15-18, 2009; Lyon, France. PS-02-008.

9. Stahl SM. Stahl’s Essential Psychopharmacology. 3rd ed. New York, NY: Cambridge University Press; 2008.

10. Hadley ME. Discovery that a melanocortin regulates sexual functions in male and female humans. Peptides. 2005;26(10):1687-1689. PubMed doi:10.1016/j.peptides.2005.01.023

11. Diamond LE, Earle DC, Rosen RC, et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res. 2004;16(1):51-59. PubMed doi:10.1038/sj.ijir.3901139

12. Rosen RC, Diamond LE, Earle DC, et al. Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT 141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra. Int J Impot Res. 2004;16(2):135-142. doi:10.1038/sj.ijir.3901200

Brainstorms is a section of The Journal of Clinical Psychiatry aimed at providing updates of novel concepts emerging from the neurosciences that have relevance to the practicing psychiatrist.

From the Neuroscience Education Institute in Carlsbad, California, and the Department of Psychiatry at the University of California San Diego, and the Department of Psychiatry at the University of Cambridge, Cambridge, United Kingdom.

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