Involvement of noradrenergic innervation from locus coeruleus to hippocampal formation in negative feedback regulation of penile erection in the rat

We demonstrated previously that a novel negative feedback mechanism for the regulation of penile erection, which is triggered by ascending sensory inputs initiated by tumescence of the penis, exists in the hippocampal formation (HF). This study further elucidated the role of the locus coeruleus (LC), which is the largest aggregate of norepinephrine-containing neurons in the brain and provides the major noradrenergic innervation to the HF, in this process. Adult male Sprague-Dawley rats that were anesthetized and maintained with chloral hydrate were used. The intracavernous pressure (ICP) recorded from the corpus cavernosum of the penis was used as the experimental index for penile erection. Electrical activation of the LC elicited a significant reduction in baseline ICP. Similar observations were obtained on microinjection bilaterally into the hippocampal CA1 or CA3 subfield or dentate gyrus of equimolar doses (5 nmol) of norepinephrine (α ₁-, α ₂-agonist), phenylephrine (α ₁-agonist), or BHT 933 (α ₂-agonist). Bilateral electrolytic lesions of the LC discernibly enhanced the magnitude and/or duration of the elevation in ICP induced by intracavernous administration of papaverine (400 μg). A potentiation of the papaverine-evoked ICP increase was also observed following pretreatment with bilateral hippocampal application of equimolar doses (250 pmol) of either prazosin (α ₁-, α _2B-, α _2C-antagonist), naftopidil (α _1A/D-antagonist), yohimbine (α ₂-antagonst), or rauwolscine (α _2B-, α _2C-antagonist). None of these antagonists, however, affected baseline ICP. These results suggest that noradrenergic innervation of the HF that originates from the LC may play an active role in negative feedback regulation of penile erection, engaging at least α _1A/D-, α _2B-, and α _2C-adrenoceptors in the HF.