Adapted Technological Platform for Screening and Identifying Compounds Capable of In vivo Spinal Network-mediated Reflex Ejaculation in Non-anesthetized, Chronic Paraplegic Mice: Evidence of Clonidine-elicited Seminal Emission

Abstract

Several drugs have been shown to facilitate locomotor rhythmogenesis and treadmill training after Spinal Cord Injury (SCI). Clonidine, an alpha-adrenoceptor agonist, is of particular interest given its well-known effects on facilitation of reflex-induced spinal stepping in acute or chronic complete low-thoracic spinal cord-transected (Tx) cats. Since locomotion and ejaculation are controlled by neuronal networks located in the same area of the spinal cord (i.e., upper- to mid-lumbar segments), we hypothesized that clonidine may have comparable effects on reflex ejaculation in low-thoracic Tx animals. To achieve that, the main aim was to adapt a technological platform developed initially for in vivo testing of pro-locomotor compounds in order to establish and validate an approach for assessing both behaviourally and quantitatively, drug-induced reflex ejaculation ex copula in an animal model of SCI. At 6 or 7 days post-Tx, male mice received a single injection of clonidine (0.005-2.5 mg/kg, i.p.). At doses ranging between 0.1 and 2.5 mg/kg, clonidine acutely induced, in 88% of cases (35/40 mice), seminal emissions as fluids or plugs (in-urethra) with no erection nor expulsion. Given that clonidine is a partial alpha-2 agonist, the results suggest that alpha-2 adrenoceptor activation is associated with seminal emission in non-copulating and non-stimulated (e.g., manually or electrically) chronic paraplegic mice. To our knowledge, this is the first report of alpha-2-mediated, clonidine-induced seminal emission.