title: Intermittent morphine administration induces a long-lasting synergistic effect of corticosterone on dopamine D1 receptor functioning in rat striatal GABA neurons.
abstract: Glucocorticoid receptor (GR)-mediated facilitation of striatal dopaminergic (DA) neurotransmission has been proposed to play a role in behavioral sensitization induced by intermittent exposure to drugs of abuse or stressors. Searching for possible common neuronal substrates acted upon by drugs of abuse and corticosterone, we addressed the question as to whether such a facilitatory effect is apparent (i.e., persists) in primary cultures of rat striatum subsequent to intermittent (prenatal) morphine administration. As previously observed in striatal slices of morphine-treated rats, intermittent morphine exposure in vivo caused a long-lasting increase in DA D1 receptor-stimulated adenylyl cyclase activity, that appeared to persist in primary cultures of rat striatal gamma-aminobutyric acid (GABA) neurons. Subsequent in vitro exposure of these striatal neurons to corticosterone or dexamethasone, simultaneously activating GR and mineralocorticoid receptors (MR), about doubled this adaptive effect of previous in vivo morphine administration. The selective MR agonist aldosterone was ineffective in this respect. Prior in vivo morphine treatment also enhanced the stimulatory in vitro effect of corticotropin releasing hormone (CRH) on adenylyl cyclase in cultured GABA neurons. However, the enhanced CRH receptor functioning was not potentiated by in vitro corticosterone exposure. Activation of GR by corticosterone did not facilitate the increase in D1 receptor efficacy induced by sustained activation of muscarinic receptors in cultured striatal neurons. These data indicate that previous intermittent morphine administration induces a long-lasting synergistic effect of corticosterone on enhanced striatal DA neurotransmission at the level of postsynaptic D1 receptors. Moreover, the induction of this neuroadaptation seems to display opioid receptor selectivity and its long-term expression may be confined to D1 receptors. Since exposure to drugs of abuse or stressors not only increase striatal DA release but also plasma corticosterone levels, we hypothesize that this adaptive phenomenon in DA-sensitive GABA neurons is involved in the expression of morphine-induced long-term behavioral sensitization to drugs of abuse and stressors.
authors.affiliation: Graduate School Neurosciences Amsterdam, Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Free University, Medical Faculty, The Netherlands.
authors.forename: A N
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: T J
authors.initials: TJ
authors.lastname: De Vries
authors.forename: L J
authors.initials: LJ
authors.lastname: Vanderschuren
authors.forename: G H
authors.initials: GH
authors.lastname: Tjon
authors.forename: P
authors.initials: P
authors.lastname: Nestby
authors.forename: G
authors.initials: G
authors.lastname: Wardeh
authors.forename: A H
authors.initials: AH
authors.lastname: Mulder
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004622:Embryo, Mammalian; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D009020:Morphine / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010095:Oxotremorine / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D004745:Enkephalins; D018019:Receptors, Corticotropin-Releasing Hormone; D017447:Receptors, Dopamine D1; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005680:gamma-Aminobutyric Acid; D010095:Oxotremorine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D009020:Morphine; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003345:Corticosterone