GALANIN RECEPTOR ANTAGONISTS ATTENUATE SPINAL ANTINOCICEPTIVE EFFECTSOF DAMGO, TRAMADOL AND NONOPIOID DRUGS IN RATS

Citation
N. Selve et al., GALANIN RECEPTOR ANTAGONISTS ATTENUATE SPINAL ANTINOCICEPTIVE EFFECTSOF DAMGO, TRAMADOL AND NONOPIOID DRUGS IN RATS, Brain research, 735(2), 1996, pp. 177-187
Citations number
52
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
00068993
Volume
735
Issue
2
Year of publication
1996
Pages
177 - 187
Database
ISI
SICI code
0006-8993(1996)735:2<177:GRAASA>2.0.ZU;2-C
Abstract
The involvement of endogenous galanin to antinociception elicited by i ntrathecally (i.t.) or systemically administered drugs from different chemical and therapeutic classes was investigated using the rat Randal l-Selitto or the rat tail-flick test, in the absence or presence of th e i.t. administered galanin receptor antagonists galantide and M-35. A ntinociception elicited by i.t. tramadol (24 mu g), DAMGO (1 mu g), cl onidine (48 mu g), desipramine (6 mu g) or fenfluramine (60 mu g) was attenuated by i.t. galantide (2 mu g); the attenuation reached signifi cance at least at one time point. A partial antagonism by i.t. galanti de was also observed against the antinociception of i.p tramadol (10 m g/kg), i.v. clonidine (1 mg/kg), i.p. desipramine (1 mg/kg), or i.p. d ipyrone (1000 mg/kg), but antinociception by i.p. fenfluramine (30 mg/ kg) was not affected. Using M-35 (2 mu g i.t.), the antinociception of i.t. tramadol or DAMGO was attenuated, but no inhibition was observed when clonidine, desipramine or fenfluramine were used i.t. If drugs w ere administered systemically, only antinociception of i.p. fenflurami ne but not that of i.p. tramadol, or i.v. clonidine, or i.p. desiprami ne or i.p. dipyrone was attenuated. In the rat tail-flick test, co-inj ection of either 2 mu g i.t. galantide or M-35 with i.t. tramadol (12 mu g) almost abolished the antinociceptive effect, whereas the antinoc iception of systemically administered tramadol (4.6 mg/kg i.p.) was on ly partially attenuated by i.t. galantide and not affected by i.t. M-3 5. Binding studies in dorsal spinal cord tissue showed no affinity of galantide or M-35 to spinal mu- or delta-, or Ic-opioid receptors and none of the other drugs interfered with the spinal galanin binding sit e. These data give further support of at least a partial galanin link in spinal processes of antinociception.