Introduction. Sexual desire is controlled by brain systems involved in sexual excitation and inhibition. Hypoactive sexual desire disorder (HSDD) may result from hypofunctional excitation, hyperfunctional inhibition, or some mix of the two.
Aim. This study aimed to identify neurochemical and neuroanatomical systems involved in sexual excitation and inhibition, their role during normal, and hypoactive sexual expressions.
Methods. A comprehensive review of the human and animal literature is made, and a theory surrounding the ways that HSDD can be manifested and treated is presented.
Main Outcome Measures. Drug effects and neural systems derived largely from rat studies that are involved in the stimulation of sexual desire (excitatory system) vs. the stimulation of sexual reward, sedation, and satiety (inhibitory system).
Results. Brain dopamine systems (incertohypothalamic and mesolimbic) that link the hypothalamus and limbic system appear to form the core of the excitatory system. This system also includes melanocortins, oxytocin, and norepinephrine. Brain opioid, endocannabinoid, and serotonin systems are activated during periods of sexual inhibition, and blunt the ability of excitatory systems to be activated.
Conclusions. Drugs that stimulate the activation of hypothalamic dopamine or that blunt endocannabinoid or serotonin release and/or postsynaptic binding may be effective in stimulating sexual desire in animals and humans. The characterization of how those drugs work will help generate a rational approach to drug development in the treatment of HSDD. Pfaus JG. Pathways of sexual desire. J Sex Med 2009;6:1506–1533.