The 5-HT1A receptor agonist 8-OH-DPAT enhances opiate-induced rigidity when applied intrathecally

University College London (2003) J Physiol 547P, C147

Oral Communications: The 5-HT1A receptor agonist 8-OH-DPAT enhances opiate-induced rigidity when applied intrathecally

M.H. Gladden, S.M. Cain, L. Johnston, N.A. Kelley and R. Thomson

Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK

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Muscle rigidity can occur during induction of anaesthesia using potent opiates (see Benthuysen et al. 1986). The opiate fentanyl initially induces apnoea, bradycardia and a fall in blood pressure when administered I.V. to urethane-anaesthetised rats. λ-Motoneurone activity is depressed, as indicated by a fall in the output of muscle spindles monitored by in-continuity recordings from muscle nerve branches. Presumably this is similar to inhibition of α-motoneurone activity by opiates (see Duggan & North, 1984). However, providing that there are no rhythmic respiratory movements for 15-55 s, λ-motoneurone activity returns strongly, accompanied by a rise in blood pressure and an exophthalmos (Gladden & Sahal, 2000; Gladden et al. 2001). Muscle contraction, indicated by EMG activity, follows the rise in λ-motoneurone activity. These changes subside when artificial ventilation is commenced, but thereafter the same responses to apnoea can be elicited repeatedly by stopping ventilation. We investigated the effect of the 5-HT1A receptor agonist 5-OH-DPAT because Jaros & Kolasiewicz (1995) reported that it abolishes opiate-induced rigidity in non-anaesthetised rats if given intraperitoneally 40 min before or 20 min after fentanyl I.P.

Six Sprague-Dawley rats were anaesthetised with urethane (170 mg 100 g-1 I.P.). In-continuity recordings were made from S1 dorsal and ventral roots and a nerve branch to the longissimus caudae muscle which supplies 4-9 spindles. The blood pressure and FET,CO2 were also monitored. After the experiments all animals were killed with an overdose of anaesthetic. Fentanyl (40 mg kg-1 I.V.) induced the sequence of changes outlined above. After 5 min of artificial ventilation, recorded variables returned to pre-opiate levels and were unchanged when 5-OH-DPAT (0.04-0.1 mg ml-1) was applied to the exposed sacral spinal cord. However, when the ventilator was stopped 5 min later, the neural responses to apnoea were increased. The mean dorsal root activity measured 40 s after initiation of apnoea was compared with the value 20 s before apnoea. It was 197 ± 22 % (mean ± S.E.M.) with fentanyl alone, but increased significantly after the administration of 5-OH-DPAT (302 ± 26 %, P < 0.01, paired t test). We suggest that 8-OH-DPAT acts supraspinally to abolish opiate-induced rigidity.



Where applicable, experiments conform with Society ethical requirements.

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