Pro-erectile effect of systemic apomorphine: existence of a spinal site of action.
OBJECTIVE
Apomorphine exerts pro-erectile effects by acting on neurons in the paraventricular nucleus of the hypothalamus. In spinal cord injured rats we assessed whether apomorphine also directly activates the spinal autonomic and somatic neurons controlling penile erection


METHODS
Intracavernous and blood pressure was monitored in groups of 10 anesthetized rats to quantify intracavernous pressure increases elicited after intravenous apomorphine. We determined the number and duration of increases, percent of maximum intracavernous pressure/mean diastolic blood pressure using the formula, maximum intracavernous pressure/diastolic blood pressure x 100, area under the intracavernous pressure curve/diastolic blood pressure and sum of the area under the curve/diastolic blood pressure.


RESULTS
Of 2, 10, 50 and 250 microg./kg. intravenous apomorphine 50 microg./kg. induced significant pro-erectile effects and was subsequently used. In spinal cord injured rats 50 microg./kg. intravenous apomorphine significantly increased median maximum intracavernous pressure/diastolic blood pressure x 100 compared with vehicle injection (56 versus 27 seconds, p <0.001), area under the curve/diastolic blood pressure (21 versus 12 seconds, p = 0.07) and the sum of area under the curve/diastolic blood pressure (132 versus 32 seconds, p = 0.01). These pro-erectile effects of apomorphine were prevented by 50 mg./kg. hexamethonium intravenously or bilateral transection of the pelvic nerves. They were not affected by 3 mg./kg. of the peripheral D1/D2 antagonist domperidone intraperitoneally. In spinal cord injured rats subcutaneous pretreatment with 0.2 mg./kg. of the D1 antagonist SCH23390 significantly enhanced apomorphine induced erections, as indicated by an area under the curve/diastolic blood pressure of 23 to 30 seconds (p = 0.003), whereas they were not changed by 25 mg./kg. of the D2 antagonist sulpiride intraperitoneally. Under the same conditions 1 mg./kg. of the central D1/D2 antagonist haloperidol intraperitoneally only reduced the number of responding rats to 5 versus 10 of 10.


CONCLUSIONS
In spinal cord injured rats systemic apomorphine elicits erection by acting at the spinal cord level. This finding suggests that systemic apomorphine elicits penile erections via spinal and supraspinal targets.
Giuliano
François
F
Groupe de Recherche en Urologie, UPRES, Medical University of Paris South, Le Kremlin Bicêtre, France.
Allard
Julien
J
Rampin
Olivier
O
Droupy
Stéphane
S
Benoit
Gérard
G
Alexandre
Laurent
L
Bernabé
Jacques
J
D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D004294:Domperidone / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000503:physiopathology; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018738:Hexamethonium; D004294:Domperidone; D013469:Sulpiride; D006220:Haloperidol; D001058:Apomorphine