Methamphetamine-induced stereotypy correlates negatively with patch-enhanced prodynorphin and arc mRNA expression in the rat caudate putamen: the role of mu opioid receptor activation

Pharmacol Biochem Behav. 2010 Jun;95(4):410-21. doi: 10.1016/j.pbb.2010.02.019. Epub 2010 Mar 15.

Abstract

Amphetamines induce stereotypy, which correlates with patch-enhanced c-Fos expression the patch compartment of caudate putamen (CPu). Methamphetamine (METH) treatment also induces patch-enhanced expression of prodynorphin (PD), arc and zif/268 in the CPu. Whether patch-enhanced activation of any of these genes correlates with METH-induced stereotypy is unknown, and the factors that contribute to this pattern of expression are poorly understood. Activation of mu opioid receptors, which are expressed by the neurons of the patch compartment, may underlie METH-induced patch-enhanced gene expression and stereotypy. The current study examined whether striatal mu opioid receptor blockade altered METH-induced stereotypy and patch-enhanced gene expression, and if there was a correlation between the two responses. Animals were intrastriatally infused with the mu antagonist CTAP (10 microg/microl), treated with METH (7.5 mg/kg, s.c.), placed in activity chambers for 3h, and then sacrificed. CTAP pretreatment attenuated METH-induced increases in PD, arc and zif/268 mRNA expression and significantly reduced METH-induced stereotypy. Patch-enhanced PD and arc mRNA expression in the dorsolateral CPu correlated negatively with METH-induced stereotypy. These data indicate that mu opioid receptor activation contributes to METH-induced gene expression in the CPu and stereotypy, and that patch-enhanced PD and arc expression may be a homeostatic response to METH treatment.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Central Nervous System Stimulants / toxicity
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism*
  • Enkephalins / genetics
  • Enkephalins / metabolism*
  • Gene Expression Regulation / drug effects
  • Genes, Immediate-Early
  • Image Processing, Computer-Assisted / methods
  • In Situ Hybridization
  • Male
  • Methamphetamine / toxicity*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Peptide Fragments / pharmacology
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Putamen / drug effects
  • Putamen / metabolism*
  • Putamen / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / antagonists & inhibitors
  • Receptors, Opioid, mu / metabolism*
  • Severity of Illness Index
  • Somatostatin / pharmacology
  • Stereotypic Movement Disorder / chemically induced
  • Stereotypic Movement Disorder / metabolism*
  • Stereotypic Movement Disorder / pathology
  • Stereotypic Movement Disorder / prevention & control
  • Time Factors

Substances

  • CTAP octapeptide
  • Central Nervous System Stimulants
  • Cytoskeletal Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Enkephalins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Opioid, mu
  • activity regulated cytoskeletal-associated protein
  • Methamphetamine
  • Somatostatin
  • preproenkephalin