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YANNICK GOUMON Y COLS. AN. R. ACAD. NAC. FARM.

It should also be noted that morphine seems to have paradoxical
effects according to its concentration. One study showed that the
subcutaneous injection of a small quantity of morphine (1-10 µg/kg)
induced hyperalgesia whereas high doses (1000-7000 µg/kg) induced
analgesia (87). These results are consistent with those of Robuvitch et
al. who showed that DAMGO, a µ receptor agonist, stimulated cAMP
production in the SK-N-SH cell line (derived from a neuroblastoma)
at a concentration of 10 nM, but inhibited it at 0.1 µM (88). One of
this group’s hypotheses is that some nociceptive neurones could be

expressing a low level of G protein-coupled µ receptors with a high
affinity for morphine, and these could be mediating the hyperalgesia
in the presence of low morphine concentrations; these same neurones
would also be expressing classic µ receptors coupled with Gi/o
proteins, to mediate the analgesia observed at the higher morphine

concentration (89).

Endogenous morphine and memory

An experiment in which antibodies against morphine were injected
into murine CSF pointed to a link between endogenous morphine and
memorisation (90): after twelve hours of fasting, control mice showed
deficient memorisation whereas memorisation processes were
unaffected in the mice in which the level of endogenous morphine had
been artificially depressed (i.e. neutralized by the antibodies).
Endogenous morphine could therefore inhibit memorisation at times
of stress (e.g. during starvation).

Exogenous morphine has been observed to have various effects
on hippocampal function, the hippocampus being known to be a
key structure in memorisation. Morphine is known to be able to
modulate neurotransmission in the hippocampus by inhibiting its
GABAergic interneurones. Such inhibition would result in an
increase in the discharge amplitude of pyramidal neurones in the
CA1 zone (91) and modify the efficacy of glutamatergic synapses by
acting on the expression of proteins important for the post-synaptic
density [i.e. receptors (92)]. Morphine would therefore act to
consolidate memories by promoting long-term potentiation (LTP).
However, other experiments have shown that prenatal exposure to

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