Synapse. 2014 Dec;68(12):634-640. doi: 10.1002/syn.21778. Epub 2014 Sep 08.

Mephedrone alters basal ganglia and limbic dynorphin systems.

Synapse (New York, N.Y.)

Christopher L German, Mario E Alburges, Amanda J Hoonakker, Annette E Fleckenstein, Glen R Hanson

PMID: 25155699 PMCID: PMC4363041 DOI: 10.1002/syn.21778

Abstract

Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pretreatment with D

© 2014 Wiley Periodicals, Inc.

Keywords: basal ganglia; dopamine; dynorphin; limbic system; mephedrone; stimulant

References

1. Pharmacol Biochem Behav. 2013 Jan;103(3):501-9 - PubMed
2. Brain Res Brain Res Rev. 1994 Jan;19(1):1-28 - PubMed
3. Synapse. 1996 Feb;22(2):114-22 - PubMed
4. Nat Neurosci. 2005 Nov;8(11):1445-9 - PubMed
5. Addict Biol. 2013 Sep;18(5):786-99 - PubMed
6. Psychopharmacology (Berl). 2004 Apr;172(4):422-9 - PubMed
7. Life Sci. 2014 Feb 27;97(1):2-8 - PubMed
8. Psychopharmacology (Berl). 2010 Jun;210(2):121-35 - PubMed
9. Psychopharmacology (Berl). 2014 Jan;231(1):199-207 - PubMed
10. Neuropsychopharmacology. 2013 Aug;38(9):1770-9 - PubMed
11. Pharmacol Rev. 2001 Dec;53(4):453-86 - PubMed
12. J Pharmacol Exp Ther. 2011 Nov;339(2):530-6 - PubMed
13. J Pharmacol Exp Ther. 1994 Jul;270(1):192-7 - PubMed
14. Trends Neurosci. 2012 Oct;35(10):587-96 - PubMed
15. J Pharmacol Exp Ther. 1990 Jun;253(3):938-43 - PubMed
16. Psychopharmacology (Berl). 2009 Sep;205(4):565-75 - PubMed
17. Psychopharmacology (Berl). 2009 Jan;201(4):517-27 - PubMed
18. Eur J Pharmacol. 1987 Dec 1;144(2):245-6 - PubMed
19. Addiction. 2011 Nov;106(11):1991-6 - PubMed
20. J Pharmacol Exp Ther. 1988 Jul;246(1):403-8 - PubMed
21. Brain Res. 1985 Apr 8;331(2):358-62 - PubMed
22. J Neurochem. 2011 May;117(3):470-8 - PubMed
23. Eur J Pharmacol. 1988 Mar 15;147(3):411-20 - PubMed
24. Drug Alcohol Depend. 2010 May 1;108(3):183-94 - PubMed
25. Eur J Pharmacol. 1988 Oct 11;155(1-2):11-8 - PubMed
26. Brain Res. 1991 Aug 2;555(2):233-8 - PubMed
27. J Neurochem. 2014 Aug;130(3):402-7 - PubMed
28. Neuropeptides. 1987 Nov-Dec;10(4):369-86 - PubMed
29. Addiction. 2012 Apr;107(4):792-800 - PubMed
30. Annu Rev Pharmacol Toxicol. 2007;47:681-98 - PubMed
31. Neuropsychopharmacology. 2012 Apr;37(5):1192-203 - PubMed
32. J Pharmacol Exp Ther. 2011 Mar;336(3):809-15 - PubMed

Publication Types

• Journal Article

Grant support

• K02 DA019447/DA/NIDA NIH HHS/United States
• R01 DA011389/DA/NIDA NIH HHS/United States
• R01 DA031883/DA/NIDA NIH HHS/United States
• R29 DA011389/DA/NIDA NIH HHS/United States