| dc.description.abstract | The aims of this study were to investigate the following:
(a) Antinociceptive effects of opioid receptor-selective drugs on
thermal pain (Hot plate test) and chemical pain (Formalin
test and Modified acetic acid test) and
(b) Behavioural effects of opioid receptor-selective drugs in the
naked mole-rat.
The study was to provide data on the roles of specific opioid receptors (mu,
delta and kappa) on nociception and sensorimotor behaviour in the naked
mole-rat, a primitive fossorial rodent.
In the hot plate test (60°C), DAMGO (mu-agonist) or DPDPE (delta
agonist) caused a naloxone-reversible decrease in the response latency,
whereas U-50488 or U-69593 (kappa agonists) caused a naloxone-reversible
increase. in the response latency. .The effects of these drugs were dose-
~>
dependant. Naloxonazine, a mu-l receptor antagonist blocked the effect of
DAMGO on the response latency. In the formalin test (20 microliters, 10%),
higher doses of DAMGO or DPDPE caused a statistically significant reduction
in the mean scratchinglbiting time in both the early and late phases of the test.
The effect was blocked by naloxone. Naloxonazine blocked the effect of
DAMGO only in the late phase. U-50488 or U-69593, at all the doses used did
not significantly change the mean scratchinglbiting time in the early phase.
However, in the late phase higher doses of these drugs caused a statistically
significant and naloxone-reversible decrease in the mean scratching/biting
time. In the modified acetic acid test, a dose-dependent naloxone-reversible
decrease in the mean wiping response was recorded following the
administrationof DAMGO, DPDPE, U-50488 or U-69593. Naloxonazine also
blockedthe effect of DAMGO in this test.
On behaviour, DAMGO (> 1 mg/kg) caused a naloxone-reversible but
not naloxonazine-reversible increase in motor activity, state of excitation and
aggressivebehaviour. All the doses of DPDPE and lower doses ofU-50488 «
1 mglkg) or U-69593 « 0.05 mg/kg) used had no significant effect on the
general behaviour of the animal. Higher doses of the kappa agonists caused an
initial sensorimotor depression that gradually gave way to motor hyperactivity,
excitationand aggression. The behavioural effects were dose-dependent.
In summary, the current results clearly showed differences in the roles
of opioid receptors on pain control and behaviour. DAMGO or DPDPE caused
hyperalgesia in the hot plate test but antinociception in the formalin test and
the modified acetic acid test, whereas-the kappa agonists (U-50488 or U-
69593) caused antinociception in all the three tests of nociception used in the
naked mole-rat. These findings had not been reported before and therefore
they provide more information on the roles of opioid system in the naked
mole-rat. Both the hyperalgesia and the antinociception were mediated by
opioid receptors as each was blocked by naloxone. It is possible that the NMethyl-
Dsaspartate (NMDA) receptors in the central nervous system may be
responsible for the opioid-induced hyperalgesia in naked mole-rat. Future use
of NMDA receptor antagonists together with opioids may explain the
mechanisms of the opioid-induced hyperalgesia in the naked mole-rat. The
results also showed that the developed orofacial model of acetic acid test is a
useful model for studying nociception and antinociception in the naked molerat.
Behavioural results showed that stimulation of kappa receptors produced,
in a dose-dependent manner, an initial sensorimotor depression and later on
marked excitation and aggression in the mole-rat, whereas stimulation of mu
opioids caused enhanced motor activity when injected at high doses only. This
suggested that kappa receptors could be crucial in initiating behavioural
changes in the naked mole-rat. The mechanisms of opioid-induced
behavioural effects are not clear at the moment. It is postulated that
dopaminergic system may be responsible for the opioid-induced behaviour in
the naked mole-rat. This is an area that needs to be investigated in future. It
appears from the present data that the naked mole-rat may be a good model for
studying opioid-induced tolerance and opioid-induced side effects commonly
seen in cancer patients chronically treated with opioids . | en |
