Effect of opioid receptor blockade on acetaldehyde self-administration and ERK phosphorylation in the rat nucleus accumbens
Alcohol. 2011-12-01; 45(8): 773-783
DOI: 10.1016/j.alcohol.2011.06.003
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We have previously shown that acetaldehyde (ACD), the first metabolite of
ethanol, regulates its motivational properties and possesses reinforcing effects
by itself. A large and still growing body of evidence indicates that the
endogenous opioidergic system plays a critical role in the motivational effects
of ethanol and suggests a role for extracellular signal-regulated kinase (ERK) in
these effects of both ethanol and ACD. The present study was undertaken to
examine if opioid-mediated mechanisms are involved in the reinforcing properties
of ACD and in ACD-elicited ERK activation. To this end, Wistar rats were trained
to orally self-administer ACD (0.2%) by nose poking. Responses on active nose
poke caused delivery of ACD solution, whereas responses on inactive nose poke had
no consequences. The effect of pretreatment with a nonselective opioid receptor
antagonist, naltrexone (NTX), was evaluated during (1) maintenance of ACD
self-administration, (2) deprivation effect after ACD extinction, and (3) ACD
self-administration under a progressive-ratio schedule of reinforcement.
Additionally, we tested the effect of NTX on saccharin (0.05%) reinforcement, as
assessed by oral self-administration, and on ACD-elicited ERK phosphorylation in
the nucleus accumbens (Acb), as assessed by immunohistochemistry. Finally, we
examined the effect of a μ(1)-selective opioid receptor antagonist, naloxonazine
(NLZ), on the maintenance phase of ACD and saccharin self-administration. The
results indicate that NTX (0.4-0.8mg/kg) reduced the maintenance, the deprivation
effect, and the break points of ACD self-administration without suppressing
saccharin self-administration. Moreover, NTX decreased ACD-elicited ERK
activation in the Acb shell and core. NLZ (10-15mg/kg) reduced the maintenance
phase of ACD self-administration without interfering with saccharin
self-administration, whereas both NTX and NLZ failed to modify responses on
inactive nose poke indicating the lack of a nonspecific behavioral activation.
Overall, these results indicate that the opioid system is implicated in the
reinforcing properties of ACD and suggest an involvement of ERK. The finding that
NTX and NLZ reduce ACD but not saccharin self-administration indicates that these
effects are specific to ACD.