Elsevier

Neuropharmacology

Volume 29, Issue 5, May 1990, Pages 463-468
Neuropharmacology

Selective serotonin1A/1B agonists differentially affect spinal nociceptive reflexes

https://doi.org/10.1016/0028-3908(90)90168-QGet rights and content

Abstract

The purpose of the present experiments was to determine whether serotonin-1A (5-HT1A) and serotonin-1B (5-HT1B) binding sites, recently characterized in the spinal cord of the rat, mediate differential effects of 5-HT on spinal nociceptive processing. Several days after spinal transection at T10, rats were injected intraperitoneally at 20 min intervals, with increasing doses (0, 0.1, 0.4, 2.0, 9.0 mgkg) of either a 5-HT1A selective agonist (8-OH-DPAT, buspirone) or a 5-HT1B agonist (mCPP, TFMPP). Nociceptive sensitivity was determined by quantifying, in cm2, changes from baseline in the receptive field areas of three spinal nociceptive withdrawal reflexes after noxious (> 400 mmHg) levels of mechanical stimulation. The 5-HT1A agonist 8-OH-DPAT and buspirone, significantly increased in a dose-dependent manner the receptive field areas of the three reflexes, with the following log ED50 values (nmolkg): ventroflexion reflex—buspirone (2.75), 8-OH-DPAT (2.70); dorsiflexion reflex—buspirone (2.91), 8-OH-DPAT (2.67); lateral flexion reflex—buspirone (3.51), 8-OH-DPAT (2.77). The hypersensitivity of the reflexes after pretreatment with buspirone was effectively blocked by the 5-HT1A selective antagonist spiperone, at all doses (0.001, 0.01, 0.1 and 1.0 mgkg) tested. The 5-HT1B selective agonists mCPP and TFMPP significantly decreased the receptive field are of the ventroflexion reflex (log ED50 values: mCPP, 3.79 nmolkg; TFMPP, 3.61 nmolkg) with no significant effect on the dorsiflexion or lateral flexion reflexes. Maximal expansion of the receptive field areas of the reflexes by the 5-HT1A agonists was approximately 125%; maximal decrease in the receptive field area of the ventroflexion reflex by the 5-HT1B agonists was approximately 80%. The greater potency of the 5-HT1A agonists may reflect their greater selectivity at the 5-HT1A binding site. The present data suggest that the 5-HT1A and the 5-HT1B receptor subtypes mediate differential effects of 5-HT on nociceptive processing in the spinal cord of the rat.

References (33)

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