Forebrain PENK and PDYN gene expression levels in three inbred strains of mice and their relationship to genotype-dependent morphine reward sensitivity.
BACKGROUND
Vulnerability to drug abuse disorders is determined not only by environmental but also by genetic factors. A body of evidence suggests that endogenous opioid peptide systems may influence rewarding effects of addictive substances, and thus, their individual expression levels may contribute to drug abuse liability.


OBJECTIVE
The aim of our study was to assess whether basal genotype-dependent brain expression of opioid propeptides genes can influence sensitivity to morphine reward.


METHODS
Experiments were performed on inbred mouse strains C57BL/6J, DBA/2J, and SWR/J, which differ markedly in responses to morphine administration: DBA/2J and SWR/J show low and C57BL/6J high sensitivity to opioid reward. Proenkephalin (PENK) and prodynorphin (PDYN) gene expression was measured by in situ hybridization in brain regions implicated in addiction. The influence of the kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI), which attenuates effects of endogenous PDYN-derived peptides, on rewarding actions of morphine was studied using the conditioned place preference (CPP) paradigm.


RESULTS
DBA/2J and SWR/J mice showed higher levels of PDYN and lower levels of PENK messenger RNA in the nucleus accumbens than the C57BL/6J strain. Pretreatment with nor-BNI enhanced morphine-induced CPP in the opioid-insensitive DBA/2J and SWR/J strains.


CONCLUSIONS
Our results demonstrate that inter-strain differences in PENK and PDYN genes expression in the nucleus accumbens parallel sensitivity of the selected mouse strains to rewarding effects of morphine. They suggest that high expression of PDYN may protect against drug abuse by limiting drug-produced reward, which may be due to dynorphin-mediated modulation of dopamine release in the nucleus accumbens.
Gieryk
Agnieszka
A
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland.
Ziolkowska
Barbara
B
Solecki
Wojciech
W
Kubik
Jakub
J
Przewlocki
Ryszard
R
D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics*; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological; D003463:Cues; D004745:Enkephalins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009021:Morphine Dependence / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D012201:Reward; D013045:Species Specificity
D004745:Enkephalins; D009292:Narcotic Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; C029992:proenkephalin; C051844:norbinaltorphimine; D009271:Naltrexone; C033660:preproenkephalin