Opiate addiction involves the development of chronic adaptive
changes in l-opioid receptors and associated pathways (e.g.
cAMP signalling) which lead to neuronal plasticity in the brain.
This study assessed the status of cAMP and mitogen-activated
protein kinase (MAPK) pathways in brains (pre-frontal
cortex) of chronic opiate addicts. In these subjects (n ¼ 24),
the immunodensities of adenylyl cyclase-I, PKA Ca, total and
phosphorylated CREB were not different from those in sex-,
age- and PMD-matched controls. Moreover, the ratio pCREB/
tCREB was similar in opiate addicts (0.74) and controls (0.76),
further indicating that opiate addiction in humans is not
associated with an upregulation of several key components of
cAMP signalling in the pre-frontal cortex. In contrast, the
components of MAPK cascade (Ras/c-Raf-1/MEK/ERK) were
decreased in the same brains. Notably, pronounced downregulations
of phosphorylated MEK (85%) and ERK1/2
(pERK1: 81%; pERK2: 80%) were quantitated in brains of
opiate addicts. Chronic morphine treatment in rats (10–
100 mg/kg for 5 days) was also associated with decreases of
pERK1/2 (59–68%) in the cortex. In SH-SY5Y cells, morphine
also stimulated the activity of pERK1/2 (2.5-fold) and the MEK
inhibitor PD98059 blocked this effect (90%). The abnormalities
of MAPK signalling might have important consequences in
the long term development of various forms of neural plasticity
associated with opiate addiction in humans.

Read more:Long-term_regulation_of_signalling_components_of_adenylyl_cyclase_and_mitogen-activated_protein_kinase_in_the_pre-frontal_cortex_of_human_opiate_addicts

(das ganze ist sehr schwierig und bedarf den Willen das ganze via Sroogle nachzubauen,

ist ne Knabberarbeit)