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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

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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 γ-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.

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Authors and Affiliations

  1. Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Graduate School Neurosciences Amsterdam, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

    Anton N. M. Schoffelmeer, George Wardeh, Patrizia Nestby, Louk J. M. J. Vanderschuren, Taco J. De Vries, Arie H. Mulder & Guno H. K. Tjon

  2. Department of Anatomy, Medical Faculty, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

    Pieter Voorn & Allert J. Jonker

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  1. Anton N. M. Schoffelmeer
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  2. Pieter Voorn
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  3. Allert J. Jonker
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  4. George Wardeh
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  5. Patrizia Nestby
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  6. Louk J. M. J. Vanderschuren
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  7. Taco J. De Vries
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  8. Arie H. Mulder
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  9. Guno H. K. Tjon
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Special issue dedicated to Dr. Eric J. Simon.

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Schoffelmeer, A.N.M., Voorn, P., Jonker, A.J. et al. 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. Neurochem Res 21, 1417–1423 (1996). https://doi.org/10.1007/BF02532383

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