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

inhibited the growth of neuronal processes in primary cultures of
hippocampal and cerebellar granule neurones in a naloxone-
dependent fashion (101), whereas morphine concentrations of
between 1 nM and 10 fM enhanced process growth in spinal cord
and cortical neurones by a factor of over 20% (101), and a low
concentration of morphine (10 pM) stimulated process elongation
in PC-12 cells (102). These effects were not reversed by naloxone
suggesting that they are mediated by special, high-affinity receptors.

In addition, a recent study showed that low doses of morphine
had beneficial effects on synaptic regeneration and reconstruction at
the nerve terminals of non-myelinated afferent fibres of the second
lamina of the spinal cord following damage to the sciatic nerve (103).

Even more recent experiments described that low morphine
concentrations (1-100 nM, 2 hours) significantly stimulated migration
in rat microglial cells exposed to ATP (acting as a chemotactic agent)
(104). Significant effects were observed from the concentration of 1
nM with peak activity observed at 100 nM. CTAP, a specific antagonist
of µ receptors, inhibited this migration. These results suggest that
endogenous morphine in the brain could modulate immune responses
in the CNS.

Endogenous morphine and addiction

Experiments in two invertebrate models, Mytulis edulis and
Homarus americanus, showed that exposure to addictive substances
(ethanol, nicotine and cocaine) stimulates a two-fold increase in
the release of endogenous morphine by the nervous system (105). A
number of groups have postulated the existence of a link between
endogenous morphine and addiction (106) although no experiments
have yet been conducted in animals.

d) Localisation and physiological roles of endogenous
d) morphine in the periphery

In the periphery, morphine has been detected in the liver and in
a hepatocyte cell line (61, 66), and in the adrenal glands of a number

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