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.
Hawcock
Anthony B
AB
Discovery Biology, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent CT139NJ, UK. tony.hawcock@pfizer.com
Dawkins
Toni E
TE
Reynolds
David S
DS
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D023421:Models, Animal; D010052:Ovariectomy; D051381:Rats; D012726:Sexual Behavior, Animal
D018491:Dopamine Agonists; D001058:Apomorphine