Introduction Ejaculation is a reflex controlled by a spinal ejaculation generator located in the lumbosacral spinal cord responsible for the coordination of genital sensory with autonomic and motor outputs that regulate ejaculation. In the male rat, a population of lumbar spinothalamic cells (LSt cells) comprises an essential component of the spinal ejaculation generator. LSt cells are activated with ejaculation, but the nature of the signal transduction pathways involved in this activation is unknown. Moreover, it is unknown if LSt cell activation is required for expression of ejaculation. Aim The current study tested the hypothesis that ejaculatory reflexes are triggered via activation of the mitogen-activated protein (MAP) kinase signaling pathway in the LSt cells. Methods Expression of phosphorylated extracellular signal-related kinases 1 and 2 (pERK) was investigated following mating behavior, or following ejaculation induced by electrical stimulation of the dorsal penile nerve (DPN) in anesthetized, spinalized male rats. Next, the effects of intrathecal or intraspinal delivery of Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor U0126 on DPN stimulation-induced ejaculation was examined. Main Outcome Measures Expression of pERK in LSt cells and associated areas was analyzed. Electromyographic recordings of the bulbocavernosus muscle were recorded in anesthetized, spinalized rats. Results Results indicate that the MAP kinase signaling pathway is activated in LSt cells following ejaculation in mating animals or induced by DPN stimulation in anesthetized, spinalized animals. Moreover, ERK activation in LSt cells is an essential trigger for ejaculation, as DPN stimulation-induced reflexes were absent following administration of MEK inhibitor in the L3-L4 spinal area. Conclusion These data provide insight into the nature of the signal transduction pathways involved in the activation of ejaculation through LSt cells. The data demonstrate that ERK activation in LSt cells is essential for ejaculation and contribute to a more detailed understanding of the spinal generation of ejaculation.
The treatment of psychiatric patients presents significant challenges to the clinical community, and a multidisciplinary approach to diagnosis and management is essential to facilitate optimal care. In particular, the neurosurgical treatment of psychiatric disorders, or “psychosurgery,” has held fascination throughout human history as a potential method of influencing behavior and consciousness. Early evidence of such procedures can be traced to prehistory, and interest flourished in the nineteenth and early twentieth century with greater insight into cerebral functional and anatomic localization. However, any discussion of psychosurgery invariably invokes controversy, as the widespread and indiscriminate use of the transorbital lobotomy in the mid-twentieth century resulted in profound ethical ramifications that persist to this day. The concurrent development of effective psychopharmacological treatments virtually eliminated the need and desire for psychosurgical procedures, and accordingly the research and practice of psychosurgery was dormant, but not forgotten. There has been a recent resurgence of interest for non-ablative therapies, due in part to modern advances in functional and structural neuroimaging and neuromodulation technology. In particular, deep brain stimulation is a promising treatment paradigm with the potential to modulate abnormal pathways and networks implicated in psychiatric disease states. Although there is enthusiasm regarding these recent advancements, it is important to reflect on the scientific, social, and ethical considerations of this controversial field.
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