Forebrain PENK and PDYN Gene Expression Levels in Three Inbred Strains of Mice and Their Relationship to Genotype-dependent Morphine Reward Sensitivity

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2009 Dec 10

PMID 19997907

Citations 22

Authors

Agnieszka Gieryk

Barbara Ziolkowska

Wojciech Solecki

Jakub Kubik

Ryszard Przewlocki

Affiliations

Soon will be listed here.

Abstract

Rationale: 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.

Objectives: 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.

Citing Articles

Olfactory Bulbectomy Model of Depression Lowers Responding for Food in Male and Female Rats: The Modulating Role of Caloric Restriction and Response Requirement.

Fattore L, Amchova P, Fadda P, Ruda-Kucerova J Biomedicines. 2023; 11(9).

PMID: 37760922 PMC: 10525806. DOI: 10.3390/biomedicines11092481.

Traumatic Stress-Induced Vulnerability to Addiction: Critical Role of the Dynorphin/Kappa Opioid Receptor System.

Leconte C, Mongeau R, Noble F Front Pharmacol. 2022; 13:856672.

PMID: 35571111 PMC: 9091501. DOI: 10.3389/fphar.2022.856672.

Sex- and Genotype-Dependent Nicotine-Induced Behaviors in Adolescent Rats with a Human Polymorphism (rs2304297) in the 3'-UTR of the 6 Gene.

Cardenas A, Bai Y, Hajy Heydary Y, Li J, Leslie F, Lotfipour S Int J Mol Sci. 2022; 23(6).

PMID: 35328565 PMC: 8948824. DOI: 10.3390/ijms23063145.

Neuropathic Pain Dysregulates Gene Expression of the Forebrain Opioid and Dopamine Systems.

Wawrzczak-Bargiela A, Ziolkowska B, Piotrowska A, Starnowska-Sokol J, Rojewska E, Mika J Neurotox Res. 2020; 37(4):800-814.

PMID: 32026358 PMC: 7085470. DOI: 10.1007/s12640-020-00166-4.

Strain and cocaine-induced differential opioid gene expression may predispose Lewis but not Fischer rats to escalate cocaine self-administration.

Valenza M, Picetti R, Yuferov V, Butelman E, Kreek M Neuropharmacology. 2016; 105:639-650.

PMID: 26777278 PMC: 4894495. DOI: 10.1016/j.neuropharm.2016.01.004.

References

Lessov C, Swan G, Ring H, Khroyan T, Lerman C . Genetics and drug use as a complex phenotype. Subst Use Misuse. 2004; 39(10-12):1515-69. DOI: 10.1081/ja-200033202. View

Berrendero F, Mendizabal V, Robledo P, Galeote L, Bilkei-Gorzo A, Zimmer A . Nicotine-induced antinociception, rewarding effects, and physical dependence are decreased in mice lacking the preproenkephalin gene. J Neurosci. 2005; 25(5):1103-12. PMC: 6725961. DOI: 10.1523/JNEUROSCI.3008-04.2005. View

Young 3rd W, Bonner T, Brann M . Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain. Proc Natl Acad Sci U S A. 1986; 83(24):9827-31. PMC: 387235. DOI: 10.1073/pnas.83.24.9827. View

Di Chiara G, North R . Neurobiology of opiate abuse. Trends Pharmacol Sci. 1992; 13(5):185-93. DOI: 10.1016/0165-6147(92)90062-b. View

Cabib S, Orsini C, Le Moal M, Piazza P . Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience. Science. 2000; 289(5478):463-5. DOI: 10.1126/science.289.5478.463. View

Herz A, Shippenberg T . Evidence that the aversive effects of opioid antagonists and kappa-agonists are centrally mediated. Psychopharmacology (Berl). 1989; 98(2):203-6. DOI: 10.1007/BF00444692. View

Yuferov V, Ji F, Nielsen D, Levran O, Ho A, Morgello S . A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain. Neuropsychopharmacology. 2008; 34(5):1185-97. PMC: 2778041. DOI: 10.1038/npp.2008.187. View

Froehlich J, Zweifel M, Harts J, Lumeng L, Li T . Importance of delta opioid receptors in maintaining high alcohol drinking. Psychopharmacology (Berl). 1991; 103(4):467-72. DOI: 10.1007/BF02244246. View

DE WAELE J, Gianoulakis C . Effects of single and repeated exposures to ethanol on hypothalamic beta-endorphin and CRH release by the C57BL/6 and DBA/2 strains of mice. Neuroendocrinology. 1993; 57(4):700-9. DOI: 10.1159/000126428. View

10.

Spanagel R, Herz A, Shippenberg T . Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci U S A. 1992; 89(6):2046-50. PMC: 48593. DOI: 10.1073/pnas.89.6.2046. View

11.

Clarke T, Krause K, Li T, Schumann G . An association of prodynorphin polymorphisms and opioid dependence in females in a Chinese population. Addict Biol. 2009; 14(3):366-70. DOI: 10.1111/j.1369-1600.2009.00151.x. View

12.

Goeders N, Lane J, Smith J . Self-administration of methionine enkephalin into the nucleus accumbens. Pharmacol Biochem Behav. 1984; 20(3):451-5. DOI: 10.1016/0091-3057(84)90284-3. View

13.

Delfs J, Zhu Y, Druhan J, Aston-Jones G . Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature. 2000; 403(6768):430-4. DOI: 10.1038/35000212. View

14.

Murphy N, Lam H, Maidment N . A comparison of morphine-induced locomotor activity and mesolimbic dopamine release in C57BL6, 129Sv and DBA2 mice. J Neurochem. 2001; 79(3):626-35. DOI: 10.1046/j.1471-4159.2001.00599.x. View

15.

Chen A, LaForge K, Ho A, McHugh P, Kellogg S, Bell K . Potentially functional polymorphism in the promoter region of prodynorphin gene may be associated with protection against cocaine dependence or abuse. Am J Med Genet. 2002; 114(4):429-35. PMC: 6148755. DOI: 10.1002/ajmg.10362. View

16.

Schroeder J, Hummel M, Simpson A, Sheikh R, Soderman A, Unterwald E . A role for mu opioid receptors in cocaine-induced activity, sensitization, and reward in the rat. Psychopharmacology (Berl). 2007; 195(2):265-72. DOI: 10.1007/s00213-007-0883-z. View

17.

Olive M, Bertolucci M, Evans C, Maidment N . Microdialysis reveals a morphine-induced increase in pallidal opioid peptide release. Neuroreport. 1995; 6(8):1093-6. DOI: 10.1097/00001756-199505300-00005. View

18.

Krishnan-Sarin S, Jing S, KURTZ D, Zweifel M, Portoghese P, Li T . The delta opioid receptor antagonist naltrindole attenuates both alcohol and saccharin intake in rats selectively bred for alcohol preference. Psychopharmacology (Berl). 1995; 120(2):177-85. DOI: 10.1007/BF02246191. View

19.

Bruchas M, Land B, Chavkin C . The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors. Brain Res. 2009; 1314:44-55. PMC: 2819621. DOI: 10.1016/j.brainres.2009.08.062. View

20.

Rebecca Glatt A, Denton K, Boughter Jr J . Variation in nicotine consumption in inbred mice is not linked to orosensory ability. Chem Senses. 2008; 34(1):27-35. PMC: 2639451. DOI: 10.1093/chemse/bjn049. View