{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T22:45:43Z","timestamp":1772664343756,"version":"3.50.1"},"reference-count":68,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,10,10]],"date-time":"2004-10-10T00:00:00Z","timestamp":1097366400000},"content-version":"vor","delay-in-days":3506,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Comparative Neurology"],"published-print":{"date-parts":[[1995,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neurons in the striatum that project to the substantia nigra contain the opioid peptide dynorphin. Stimulation of D1 dopamine receptors results in increased expression of mRNA encoding dynorphin as well as expression of immediate\u2010early genes such as <jats:italic>c\u2010fos<\/jats:italic> in these neurons. Levels of dynorphin vary in different regions of the normal rat striatum, being highest in ventral and medial striatum. In a prior study, we have shown that both regional and temporal patterns of <jats:italic>c\u2010fos<\/jats:italic> induction following treatment with the indirect dopamine receptor agonist cocaine are inversely related to those of dynorphin expression. These results suggested that dynorphin is involved in regulating the responsiveness of these neurons to dopamine input. In the present experiments, we examined such a potential role for dynorphin by analyzing the influence of the dynorphin (kappa opioid receptor) agonist spiradoline on immediate\u2010early gene induction by cocaine, and we determined that this immediate\u2010early gene response is mediated by D1 dopamine receptors located in the striatum. As a marker of neuron activation, expression of <jats:italic>c\u2010fos<\/jats:italic> and <jats:italic>zif 268<\/jats:italic> immediate\u2010early genes was assessed with quantitative in situ hybridization histochemistry. Results showed that (1) intrastriatal infusion of the D1 dopamine receptor antagonist SCH\u201023390 (2.5\u2013250 pmol) resulted in a dose\u2010dependent blockade of immediate\u2010early gene induction by cocaine (30 mg\/kg); (2) systemic administration of the kappa opioid receptor agonist spiradoline (0.5\u201310.0 mg\/kg) decreased cocaine\u2010induced expression of <jats:italic>c\u2010fos<\/jats:italic> and <jats:italic>zif 268<\/jats:italic> mRNAs in striatum in a dose\u2010dependent manner; (3) intrastriatal infusion of spiradoline (1\u201350 nmol) also suppressed immediate\u2010early gene induction by cocaine, demonstrating that kappa opioid receptors located in the striatum mediate such an effect; and (4) systemic and intrastriatal administration of spiradoline also affected immediate\u2010early gene expression in cortex. These results demonstrate that, in striatum, immediate\u2010early gene induction by cocaine is a D1 dopamine receptor\u2010mediated process that is inhibited by activation of kappa opioid receptors. Therefore, these findings suggest that the striatal dynorphin opioid system acts directly and\/or indirectly to inhibit dopamine input to striatonigral neurons through kappa opioid receptor\u2010mediated processes in the striatum. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.903530204","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T22:15:21Z","timestamp":1104617721000},"page":"200-212","source":"Crossref","is-referenced-by-count":89,"title":["Dynorphin opioid inhibition of cocaine\u2010induced, D1 dopamine receptor\u2010mediated immediatem\u2010early gene expression in the striatum"],"prefix":"10.1002","volume":"353","author":[{"given":"Heinz","family":"Steiner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R.","family":"Gerfen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,10]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0021-9258(17)31264-4","article-title":"K Opiate agonists inhibit Ca2+ influx in rat spinal cord\u2010dorsal root ganglion cocultures","volume":"264","author":"Attali B.","year":"1989","journal-title":"J. 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