Summary
The antinociceptive activity of morphine was determined in rats using the vocalisation test, whereby vocalisation was elicited by electrical stimulation of the tail. The effects of various drugs were compared with the corresponding changes in brain amine concentration.
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1.
Manipulation of 5-hydroxytryptamine (5-HT) levels with parachlorophenylalanine (PCPA) or 5-hydroxytryptophan (5-HTP) did not modify the effect of morphine.
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2.
Catecholamine (CA)-depleting agents antagonized the effect of morphine. α-methyl-p-tyrosine (α-MT) treatment attenuated the morphine effect and decreased the CA levels, whereas the stimulation threshold before morphine administration was not changed. Inhibition of noradrenaline (NA) synthesis by FLA-63 also reduced the morphine effect.
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3.
Intraventricular injections of 5-HT, NA and dopamine (DA) (without morphine) did not alter the nociceptive threshold. The effect of morphine was not altered by 5-HT or DA.
NA attenuated the action of morphine when injected intraventricularly after morphine, but not when injected before morphine. The reduced activity of morphine in rats treated with α-MT could not be restored by intraventricular injection of NA or DA.
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4.
The concentration of morphine in brain was not altered by the α-MT treatment.
It is suggested that the antinociceptive activity of morphine as tested by this method depends on the concentration of CA in brain, NA being more important than DA. 5-HT does not seem to be involved. Apparently the antinociceptive effect of morphine does not follow a single mechanism since the putative transmitter substances play a different role depending on the animal species and test methods used.
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Reinhold, K., Bläsig, J. & Herz, A. Changes in brain concentration of biogenic amines and the antinociceptive effect of morphine in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 69–80 (1973). https://doi.org/10.1007/BF00501864
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DOI: https://doi.org/10.1007/BF00501864