title: Morphine-induced increase in D-1 receptor regulated signal transduction in rat striatal neurons and its facilitation by glucocorticoid receptor activation: possible role in behavioral sensitization.
abstract: One month (but not 1-3 days) after intermittent morphine administration, the hyperresponsiveness of rats toward the locomotor effects of morphine and amphetamine was associated with an increase in dopamine (DA) D-1 receptor-stimulated adenylyl cyclase activity and enhanced steady state levels of preprodynorphin gene expression in slices of the caudate/putamen and nucleus accumbens. Such an enduring increase in postsynaptic D-1 receptor efficacy also occurred in cultured gamma-aminobutyric acid (GABA) neurons of the striatum obtained from rats prenatally treated with morphine. Interestingly, in vitro glucocorticoid receptor activation in these cultured striatal neurons by corticosterone potentiated this neuroadaptive effect of prior in vivo morphine exposure. Since activation of glucocorticoid receptors by corticosterone did not affect D-1 receptor functioning in cultured neurons of saline-pretreated rats, prior intermittent exposure to morphine (somehow) appears to induce a long-lasting state of corticosterone hyperresponsiveness in striatal neurons. Therefore, DA-sensitive striatal GABA neurons may represent common neuronal substrates acted upon by morphine and corticosterone. We hypothesize that the delayed occurrence of these long-lasting morphine-induced neuroadaptive effects in GABA/dynorphin neurons of the striatum is involved in the enduring nature of behavioral sensitization to drugs of abuse and cross-sensitization to stressors.
authors.affiliation: Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, The Netherlands.
authors.forename: A N
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: P
authors.initials: P
authors.lastname: Voorn
authors.forename: A J
authors.initials: AJ
authors.lastname: Jonker
authors.forename: G
authors.initials: G
authors.lastname: Wardeh
authors.forename: P
authors.initials: P
authors.lastname: Nestby
authors.forename: L J
authors.initials: LJ
authors.lastname: Vanderschuren
authors.forename: T J
authors.initials: TJ
authors.lastname: De Vries
authors.forename: A H
authors.initials: AH
authors.lastname: Mulder
authors.forename: G H
authors.initials: GH
authors.lastname: Tjon
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002421:Caudate Nucleus / Q000502:physiology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology; D004399:Dynorphins / Q000096:biosynthesis; D004622:Embryo, Mammalian; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000502:physiology; D011247:Pregnancy; D011498:Protein Precursors / Q000096:biosynthesis; D011699:Putamen / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015398:Signal Transduction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D011498:Protein Precursors; D017447:Receptors, Dopamine D1; D011965:Receptors, Glucocorticoid; C036448:pre-prodynorphin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004399:Dynorphins; D009020:Morphine; D000661:Amphetamine; D000262:Adenylyl Cyclases; D003345:Corticosterone