A DUAL EFFECT OF 5-HT1B RECEPTOR STIMULATION ON NOCICEPTIVE DORSAL HORN NEURONS IN RATS

In this study the modulatory effects of 5-HT1B receptor activation on wide dynamic range neurones in the spinal cord were studied. Extracell ular single unit recordings of dorsal horn neurones were performed in intact urethane-anaesthetized female Sprague-Dawley rats, and the rece ptive field distally on one hind paw was electrically stimulated with needle electrodes applied to the skin. The 5-H(1B)receptor agonist, CP -93,129 6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one), the 5-HT1A/ B receptor antagonist cyanopindolol, and the 5-HT1A receptor antagonis t WAY100635 zinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide trihydr ochloride), were applied directly onto the spinal cord, and single uni t responses were counted separately for A beta-, A delta, C-fibre resp onses and post-discharge according to the latencies. A dual effect of CP-93,129 was observed: 50 nmol CP-93,129 caused a clear inhibition of the A delta-fibre responses, whereas 50 and 150 nmol CP-93,129 produc ed a dose-dependent increase in post-discharge without affecting A bet a- and C-fibre responses. Application of 50 nmol cyanopindolol or 50 n mol WAY100635 alone did not affect neither the neuronal A-fibre nor th e C-fibre responses, but when 50 nmol cyanopindolol was coadministered with 50 nmol CP-93,129 the effect of CP-93,129 alone was blocked: the A delta-fibre response was not inhibited and the post-discharge was n ot increased. In contrast, 50 nmol WAY100635 did not block the effect of 50 nmol CP-93,129 when the two drugs were coadministered. These res ults suggest that stimulation of the 5-HT1B receptors may have both pr o-and antinociceptive effects on wide dynamic range neurones in the do rsal horn after repeated electrical stimulation. (C) 1997 Elsevier Sci ence B.V.