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Role of prefrontal dopaminergic neurotransmission in glucocorticoid receptor‐mediated modulation of methamphetamine‐induced hyperactivity
Author(s) -
Ago Yukio,
Arikawa Shinsuke,
Yata Miyuki,
Yano Koji,
Abe Michikazu,
Takuma Kazuhiro,
Matsuda Toshio
Publication year - 2009
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20575
Subject(s) - meth , nucleus accumbens , methamphetamine , prefrontal cortex , dopaminergic , glucocorticoid receptor , chemistry , dopamine , neurotransmission , endocrinology , medicine , glucocorticoid , corticosterone , extracellular , mesolimbic pathway , pharmacology , neuroscience , receptor , psychology , ventral tegmental area , biochemistry , hormone , cognition , monomer , organic chemistry , acrylate , polymer
Abstract Glucocorticoids are involved in psychostimulant‐induced hyperactivity, but the exact mechanism is not known. This study used the selective glucocorticoid receptor antagonist, RU‐43044, to determine whether prefrontal neurotransmission is involved in glucocorticoid‐mediated modulation of methamphetamine (METH)‐induced hyperactivity in mice. Pretreatment with RU‐43044 (10–30 mg/kg) attenuated the increased spontaneous locomotor activity induced by METH (1–2 mg/kg). The psychostimulant effect of METH was also attenuated by adrenalectomy. RU‐43044 inhibited METH‐induced increases in extracellular dopamine (DA), but not serotonin (5‐HT), levels in the prefrontal cortex, but did not affect METH‐induced increases in extracellular DA levels in the nucleus accumbens shell, although it inhibited increases in extracellular 5‐HT levels. Adrenalectomy also attenuated the METH‐induced increases in extracellular DA levels in the prefrontal cortex. RU‐43044 did not affect METH‐induced increases in plasma corticosterone levels. These findings suggest that glucocorticoid receptors are involved in METH‐induced hyperactivity, and that prefrontal dopaminergic neurotransmission plays a role in glucocorticoid‐mediated modulation of METH‐induced behavioral changes. Synapse 63:7–14, 2009. © 2008 Wiley‐Liss, Inc.