Changes In Mouse Serotonin And Dopamine Receptor Labeling In The Intermediolateral Nucleus After Spinal Cord Injury

Autonomic dysreflexia (AD), a neurological condition associated with spinal cord injury (SCI), is a hypertensive crisis initiated following activation of peripheral pain fibers. As descending monoaminergic neuromodulatory transmitter systems project densely to thoracic spinal cord sympathetic preganglionic regions, lost connections after SCI may contribute to altered autonomic function. Using immunohistochemistry (IHC), this study examined the distributions of three receptors; serotonergic 5HT2A, and dopaminergic D2 and D3 in the intermediolateral nucleus (IML), the location of sympathetic preganglionic neurons (SPNs) in a mouse model of AD. Labeling was explored in control cords at ~P70, and in littermates 3 weeks following spinalization at high thoracic levels (T1/T2). Analysis focused on SPNs in the IML, efferent neurons that are presumably responsible for blood pressure increases. In controls, IHC showed labeling of processes adjacent to the IML for 5HT2A receptors and somatic/perisomatic labeling of SPNs for D2 and D3 receptors. In injured mice, D2 and D3 receptor expression significantly decreased below the injury, both close to the injury site (thoracic levels T2–T7) as well as caudally distant from the injury site (thoracic level T9–T12) (p<0.01). Though 5HT2A receptor expression was also decreased at more rostral thoracic regions (p<0.01), expression increased in a rostrocaudal gradient, with expression levels in the lower thoracic cord comparable to controls (p=.081). 5HT2A receptors can be constitutively active and facilitate sympathetic motor output. We hypothesize that their constitutive activity, unrestrained by descending inhibitory influences that include actions on D2 and D3 receptors, help support a substrate for afferent‐induced overactivation of SPNs in AD. This work is funded by the Department of Defense, SC090469.