title: Activation of mu opioid receptors in the striatum differentially augments methamphetamine-induced gene expression and enhances stereotypic behavior.
abstract: Mu opioid receptors are densely expressed in the patch compartment of striatum and contribute to methamphetamine-induced patch-enhanced gene expression and stereotypy. To further elucidate the role of mu opioid receptor activation in these phenomena, we examined whether activation of mu opioid receptors would enhance methamphetamine-induced stereotypy and prodynorphin, c-fos, arc and zif/268 expression in the patch and/or matrix compartments of striatum, as well as the impact of mu opioid receptor activation on the relationship between patch-enhanced gene expression and stereotypy. Male Sprague-Dawley rats were intrastriatally infused with d-Ala(2)-N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO; 1 μg/μL), treated with methamphetamine (0.5 mg/kg) and killed at 45 min or 2 h later. DAMGO augmented methamphetamine-induced zif/268 mRNA expression in the patch and matrix compartments, while prodynorphin expression was increased in the dorsolateral patch compartment. DAMGO pre-treatment did not affect methamphetamine-induced arc and c-fos expression. DAMGO enhanced methamphetamine-induced stereotypy and resulted in greater patch versus matrix expression of prodynorphin in the dorsolateral striatum, leading to a negative correlation between the two. These findings indicate that mu opioid receptors contribute to methamphetamine-induced stereotypy, but can differentially influence the genomic responses to methamphetamine. These data also suggest that prodynorphin may offset the overstimulation of striatal neurons by methamphetamine.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia 31207, USA. horner_ka@mercer.edu
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Horner
authors.forename: John C
authors.initials: JC
authors.lastname: Hebbard
authors.forename: Anna S
authors.initials: AS
authors.lastname: Logan
authors.forename: Golda A
authors.initials: GA
authors.lastname: Vanchipurakel
authors.forename: Yamiece E
authors.initials: YE
authors.lastname: Gilbert
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004334:Drug Administration Schedule; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D003598:Cytoskeletal Proteins; D018765:Dopamine Uptake Inhibitors; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004745:Enkephalins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; C092069:activity regulated cytoskeletal-associated protein; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D008694:Methamphetamine; C033660:preproenkephalin