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
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.