Activation of lumbosacral 5‐HT 2C receptors induces bursts of rhythmic activity in sympathetic nerves to the vas deferens in male rats

1 We previously demonstrated that p ‐chloroamphetamine (PCA) intravenously (i.v.) evokes a specific patterned bursting response in the vas deferens nerve (VDN) of anaesthetised male rats that is associated with contraction of the vas deferens, and ejaculation and contraction of the bulbospongiosus muscles. The present study used selective 5‐HT agonists to induce similar rhythmic bursting responses in the VDN in order to reveal the 5‐HT receptor subtypes involved. 2 The 5‐HT 2C receptor agonist (1.0 mg kg −1 Ro600175 i.v.) evoked the characteristic bursting pattern responses in the VDN. The 5‐HT 1A receptor agonist (1.0 mg kg −1 8‐OH‐DPAT i.v.) failed to elicit any responses. However, 8‐OH‐DPAT coadministered in combination with Ro600175 induced a potentiation of the responses. 3 Responses were also evoked in rats with a mid‐thoracic spinalisation, with a more predictable response being observed following the combination of agonists. This suggests an action of both agonists in the lumbosacral spinal cord. 4 Responses were blocked by 0.5 mg kg −1 SB206553 i.v. (5‐HT 2B/C receptor antagonist) or 0.5 mg kg −1 WAY100635 i.v. (5‐HT 1A receptor antagonist), but not 0.1 or 1.0 mg kg −1 SB269970 i.v. (5‐HT 7 receptor antagonist). 5 We suggest that activation of 5‐HT 2C and 5‐HT 1A receptor subtypes synergistically elicits contraction of the vas deferens through the activation of sympathetic preganglionic neurones in the spinal cord. 6 These data support the idea of a proejaculatory action of 5‐HT 2C receptors in the lumbosacral spinal cord, suggesting a descending 5‐HT excitatory pathway in addition to a 5‐HT inhibitory pathway. An excitatory action of 8‐OH‐DPAT at lumbosacral sites is also evident.British Journal of Pharmacology (2006) 148 , 1083–1090. doi: 10.1038/sj.bjp.0706814