The Effect of the 5-HT _2A/2C Receptor Agonist DOI on Micturition in Rats with Chronic Spinal Cord Injury

Abstract

High frequency oscillation seems to reflect external urethral sphincter burst activity during voiding. Bladder voiding efficiency and high frequency oscillation activity were decreased in spinal cord injured rats. High frequency oscillation activity can be enhanced by 5-HT2A receptor agonism, improving voiding efficiency. To our knowledge it remains to be studied whether these results may have implications for the future treatment of voiding dysfunction in patients with spinal cord injury.

Serotonin (5‐HT)2A/2C receptor agonist (2,5‐dimethoxy‐4‐idophenyl)‐2‐aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat

“… proposed that the L3–L4 spinal segment may have a specific role in mediating EUS bursting activity and regulating the pelvic‐EUS reflex arc in normal rats. The DOI‐evoked facilitation of EUS bursting activity also occured in rats after chronic transection of the spinal cord at the mid‐thoracic level, which is clearly dependent on activation of 5‐HT2A receptors in the lumbosacral spinal cord .…”

Chronic spinal cord injury causes upregulation of serotonin (5‐HT)2A and 5‐HT2C receptors in lumbosacral cord motoneurons

“…The detailed cystometric method has been described previously . After the urinary bladder was exposed by a midline abdominal incision, a catheter (PE‐50 Smiths Medical) was inserted through the top of the bladder to measure the intravesical pressure (IVP) of the bladder.…”

“…In a previous study, the involvement of the 5‐HT 2A receptor in spinal micturition control was demonstrated in urethane‐anaesthetized chronic spinal cord injured rats, in which i.v. administration of the 5‐HT 2A/2C receptor agonist 2,5‐methoxy‐4‐iodoamphetamine (DOI), stimulated high frequency oscillations (HFOs) and micturition ; however, the molecular mechanisms that lead to these observed changes remain poorly understood. We tried to clarify this by using i.t.…”

Transsynaptic tracing to dissect supraspinal serotonergic input regulating the bladder reflex in rats

“…Subsequently, distinct subtypes of 5‐HT receptors were characterized not only in supraspinal sites but also in the spinal cord, indicating central 5‐HT mechanisms involved at multiple levels in the nervous system. Previous studies showed that, in the rat spinal cord, stimulating 5‐HT 1A receptors had an excitatory physiological role in the control of bladder function whereas activation of 5‐HT 2A receptors inhibited the reflex . Thus, serotonin is an important contributor to the modulation of LUT function along with other neurotransmitters.…”

“…Previous studies showed that, in the rat spinal cord, stimulating 5-HT 1A receptors had an excitatory physiological role in the control of bladder function whereas activation of 5-HT 2A receptors inhibited the reflex. 7,8 Thus, serotonin is an important contributor to the modulation of LUT function along with other neurotransmitters.…”