Journal article
Antinociception produced by systemic R(+)-baclofen hydrochloride is attenuated by CGP 35348 administered to the spinal cord or ventromedial medulla of rats
Brain research, Vol.718(1), pp.129-137
1996
DOI: 10.1016/0006-8993(96)00100-X
PMID: 8773775
Abstract
This study examined the sites in the central nervous system at which subcutaneously-administered R(+) - baclofen hydrochloride (baclofen), the most active isomer of this prototypic γ-aminobutyric acid (GABAB receptor agonist, acts to produce antinociception in the rat. To determine whether baclofen acts in the spinal cord, either saline or the GABAB receptor antagonist CGP 35348 was injected intrathecally in rats pretreated 24 min earlier with 1 or 3 mg/kg s.c. baclofen. Intrathecal (i.t.) injection of 3 or 10 μg of CGP 35348 antagonized the increase in tail-flick and hot-plate latency produced by either dose of baclofen. To determine whether baclofen acts at sites in the ventromedial medulla (VMM), either saline or CGP 35348 was microinjected in the nucleus raphe magnus or nucleus reticularis gigantocellularis pars a of rats pretreated 24 min earlier with 1 or 3 mg/kg s.c. baclofen. Microinjection of 0.5 or 3 μg of CGP 35348 at sites in the VMM produced at best only a very modest attenuation of the antinociceptive effects of baclofen. These data suggest that systemically-administered baclofen acts at sites in both the spinal cord and the VMM, but that its antinociceptive effects are likely to be mediated to a greater extent by a spinal, rather than medullary site of action. However, a definitive comparison of the relative contribution of GABAB receptors in these two regions is precluded by differences in the diffusion and concentrations of the antagonist in the spinal cord and brainstem. Finally, microinjection of 0.5 or 3.0 μg of CGP 35348 in the nucleus raphe magnus or nucleus reticularis gigantocellularis pars a of saline-pretreated rats did not alter tail-flick or hot-plate latency. This finding suggests that, unlike GABA
A receptors, GABAB receptors do not mediate the tonic GABAergic input to neurons in these nuclei.
Details
- Title: Subtitle
- Antinociception produced by systemic R(+)-baclofen hydrochloride is attenuated by CGP 35348 administered to the spinal cord or ventromedial medulla of rats
- Creators
- David A ThomasIsabel M NavarreteBrent A GrahamMalcolm K McGowanDonna L Hammond
- Resource Type
- Journal article
- Publication Details
- Brain research, Vol.718(1), pp.129-137
- Publisher
- Elsevier B.V
- DOI
- 10.1016/0006-8993(96)00100-X
- PMID
- 8773775
- ISSN
- 0006-8993
- eISSN
- 1872-6240
- Language
- English
- Date published
- 1996
- Academic Unit
- Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
- Record Identifier
- 9984006490602771
Metrics
34 Record Views