The Journal of Neuroscience, November 1, 2002, 22(21):9210-9220
Changes in Spinal
and
Opioid Systems in Mice Deficient in
the A2A Receptor Gene
Alexis
Bailey1,
Catherine
Ledent2,
Mary
Kelly1,
Susanna M. O.
Hourani1, and
Ian
Kitchen1
1 Pharmacology Group, School of Biomedical and Life
Sciences, University of Surrey, Guildford, Surrey, GU2 7XH United
Kingdom, and 2 Institut de Recherche Interdisciplinaire en
Biologie Humaine et Nucléaire, Université Libre de
Bruxelles, B-1070 Brussels, Belgium
A large body of evidence indicates important
interactions between the adenosine and opioid systems in regulating
pain at both the spinal and supraspinal level. Mice lacking the
A2A receptor gene have been developed successfully,
and these animals were shown to be hypoalgesic. To investigate whether
there are any compensatory alterations in opioid systems in mutant
animals, we have performed quantitative autoradiographic mapping of
µ,
,
, and opioid receptor-like (ORL1) opioid receptors
in the brains and spinal cords of wild-type and homozygous
A2A receptor knock-out mice. In addition, µ-,
-, and

mediated antinociception using the tail immersion test was tested
in wild-type and homozygous A2A receptor knock-out mice. A
significant reduction in [3H]deltorphin-I binding
to
receptors and a significant increase in
[3H]CI-977 binding to
receptors was detected
in the spinal cords but not in the brains of the knock-out mice. µ and ORL1 receptor expression were not altered significantly. Moreover,
a significant reduction in
-mediated antinociception and a
significant increase in
-mediated antinociception were detected in
mutant mice, whereas µ-mediated antinociception was unaffected.
Comparison of basal nociceptive latencies showed a significant
hypoalgesia in knock-out mice when tested at 55°C but not at 52°C.
The results suggest a functional interaction between the spinal
and
opioid and the peripheral adenosine system in the control of pain pathways.
Key words:
A2A knock-out; µ opioid receptor;
opioid receptor;
opioid receptor; ORL1 receptor; autoradiography; opioid-mediated antinociception
Copyright © 2002 Society for Neuroscience 0270-6474/02/22219210-11$05.00/0