Assessment of 'active investigation' as a potential measure of female sexual incentive motivation in a preclinical non-contact rodent model: observations with apomorphine.

Clinical studies have suggested therapeutic potential for the non-selective dopamine receptor agonist apomorphine, in treating female sexual dysfunction. However, experimental data suggest apomorphine may inhibit sexual behaviour in female rats. The aims of this study were: evaluate an alternate behavioural endpoint in a conscious, non-contact model of sexual behaviour; and secondly investigate apomorphine in this model. Proceptive behaviour was determined in sexually naïve ovariectomised female rats as time spent actively investigating an inaccessible sexual incentive (sexually vigorous intact male rat) relative to time investigating a social incentive (castrated male rat) in an open field arena. Apomorphine (10, 30 and 100 microg/kg SC) induced a dose-related bell-shaped increase in proceptive behaviour, achieving significance (P<0.05) at 30 microg/kg, in females given a low (estrogen 1 microg/rat+progesterone 100 microg/rat) hormonal prime. This was equivalent to proceptive activity displayed by females given a high (estrogen 5 microg/rat+progesterone 250 microg/rat) hormonal prime in full behavioural oestrous. In contrast, in females given the high hormonal prime all doses tended to decrease proceptive activity. This study demonstrates that pro-sexual effects of apomorphine are critically dependent on hormone levels; sexual motivation is enhanced in animals given a low hormonal prime, but attenuated when given to animals in behavioural oestrous.

I. Slow oscillations in vaginal blood flow: alterations during sexual arousal in rodents and humans.

PURPOSE: This study investigated slow oscillatory rhythms in vaginal blood flow as a physiological marker of female sexual arousal in rodents, human healthy volunteers, and women with female sexual arousal disorder (FSAD). MATERIALS AND METHODS: Vaginal blood flow was measured in urethane-anesthetized rodents using laser Doppler flowmetry, while in humans, vaginal photoplethysmography was used. Acquired data were filtered for frequency analysis in the range of 0.013-2.5 Hz in rodents and 0.01-0.5 Hz in humans. Rodents were assessed for changes in a high frequency range (HF = 0.6-2.5 Hz), and a low frequency range (LF = 0.013-0.6 Hz). Human data were assessed for total spectral power in the entire frequency range. RESULTS: During naturally induced arousal (exposure to male), oscillatory rhythms in vaginal blood flow from rodents demonstrated an increase in the ratio of LF oscillations to HF oscillations (LF/HF ratio). Drugs known to induce sexual arousal (apomorphine and melanotan II) were tested in anesthetized rodents. Both compounds induced an increase in the LF/HF ratio. In humans, visual sexual stimulation induced an increase in the total power of slow oscillatory activity in vaginal blood flow in healthy human volunteers. No such increase was observed in women with FSAD. CONCLUSIONS: This study demonstrated that slow oscillations in vaginal blood flow are correlated with subjective physiological arousal and display diminished responsiveness in women with FSAD. Slow oscillations in vaginal blood flow are entirely independent of vaginal vasocongestion as women with FSAD demonstrated a normal vasocongestion response to visual sexual stimulation. In conditions where rodents would be expected to be sexually aroused, slow oscillations in vaginal blood flow showed a shift from HFs to LFs. This technique will greatly enhance the investigation of female sexual function both clinically and preclinically.