Effect of ethanol self-administration on mu- and delta-opioid receptor-mediated G-protein activity.
BACKGROUND
This study examined the effects of ethanol self-administration on mu- and delta-opioid receptor-mediated G-protein activity in specific brain regions of male Long Evans rats.


METHODS
Rats were trained to self-administer ethanol by using a home-cage modification of the sucrose substitution paradigm. After 30 to 40 days of sucrose or sucrose/15% ethanol self-administration (20 min sessions, Monday-Friday), rats were killed for autoradiographic assays. Coronal sections of brains from sucrose and ethanol self-administering rats were collected and processed for basal and mu- and delta-stimulated [35S]guanosine-5'-O-(gamma-thio)-triphosphate (GTPgammaS) binding. Sections were exposed to film and then analyzed by using computer-assisted densitometry to determine levels of basal and agonist-stimulated [35S]GTPgammaS binding.


RESULTS
Mu-opioid-stimulated [35S]GTPgammaS binding was decreased in the prefrontal cortex of brains from ethanol compared with sucrose self-administering rats. Mu-opioid-stimulated [35S]GTPgammaS binding was unchanged in the cingulate cortex, caudate-putamen, nucleus accumbens, amygdala, hypothalamus, thalamus, and locus ceruleus of ethanol compared with sucrose self-administering rats. Basal and delta-opioid-stimulated [35S]GTPgammaS binding did not differ between the two groups in the prefrontal cortex or any other region analyzed.


CONCLUSIONS
These data demonstrate decreased mu-opioid-mediated G-protein activity in the prefrontal cortex of ethanol self-administering rats and suggest an interaction between ethanol and mu-opioid receptors in this region.
Sim-Selley
Laura J
LJ
Department of Pharmacology and Toxicology and Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298, USA. ljsimsel@hsc.vcu.edu
Sharpe
Amanda L
AL
Vogt
Leslie J
LJ
Brunk
Leah K
LK
Selley
Dana E
DE
Samson
Herman H
HH
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology*; D012646:Self Administration / Q000706:statistics & numerical data
D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000431:Ethanol; D019204:GTP-Binding Proteins