Pilocarpine treatments differentially affect alpha(2)-adrenoceptors which modulate the firing rate of locus coeruleus neurones and the synthesis and release of noradrenaline in rat brain
Ma. Garro et al., Pilocarpine treatments differentially affect alpha(2)-adrenoceptors which modulate the firing rate of locus coeruleus neurones and the synthesis and release of noradrenaline in rat brain, PHARM TOX, 85(2), 1999, pp. 74-79
We have investigated the effect of treatments with the muscarinic acetylcho
line receptor agonist, pilocarpine, on the sensitivity of central alpha(2)-
adrenoceptors that regulate the firing activity of rat locus coeruleus, the
tyrosine hydroxylase activity in the rat cortex, hippocampus and hypothala
mus, and the K+-evoked release of [H-3]noradrenaline from rat cortical and
hippocampal synaptosomes. Short-term (4 days), but not acute, treatment wit
h pilocarpine caused a small but statistically significant increase in the
inhibitory effect of the alpha(2)-adrenoceptor agonist clonidine on the fir
ing rate of locus coeruleus neurones, with a decrease in the ED50 Of 29% (P
<0.001). However, no change in the effect of clonidine on the locus coerule
us was observed after longer pilocarpine(ll days) treatment. In the rat cer
ebral cortex, but not in hippocampus or hypothalamus, chronic (19 days) tre
atment with pilocarpine caused a decrease in the inhibitory effect of cloni
dine on tyrosine hydroxylase activity (55%, P<0.05), but did not change the
stimulatory effect of the alpha(2)-adrenoceptor antagonist idazoxan. Moreo
ver, treatments (4, 11 and 19 days) with pilocarpine did not alter the inhi
bitory effect of clonidine [10(-8)-10(-5) RI] on the K+-evoked release of [
H-3]noradrenaline from rat cortical and hippocampal synaptosomes. These res
ults indicate that administration of pilocarpine slightly potentiates some
but not all the functional responses mediated by brain presynaptic alpha(2)
-adrenoceptors. In conclusion, these results do not support the hypothesis
that chronic treatments with pilocarpine lead to a suitable model of alpha(
2)-adrenoceptor supersensitivity.