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Methamphetamine‐induced sensitization includes a functional upregulation of ventral pallidal 5‐HT 2A/2C receptors
Author(s) -
Napier T. Celeste,
Istre Erik D.
Publication year - 2008
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.20460
Subject(s) - meth , methamphetamine , serotonergic , downregulation and upregulation , agonist , serotonin , pharmacology , receptor , sensitization , chemistry , neuroscience , medicine , biology , biochemistry , monomer , organic chemistry , acrylate , gene , polymer
Methamphetamine (METH) causes the release of serotonin (5‐HT), but little is known about how repeated exposure to METH modifies serotonergic receptor function, especially in the ventral pallidum (VP), a brain region highly innervated by serotonin inputs. The current study was designed to ascertain if ventral pallidal neurons are functionally upregulated 3 days after a behaviorally sensitizing treatment regimen of METH, and whether these effects could be revealed by activating the 5‐HT 2A/2C receptors. Rats treated with METH (2.5 kg/mg/day) for 5 days, responded with enhanced stereotypic behaviors. Electrophysiological evaluations of the VP conducted in anesthetized rats 3 days following this sensitizing treatment regimen of METH revealed that spiking rate increases induced by intravenous METH were augmented above that seen in rats with a history of saline treatments. The efficacy of the 5‐HT 2A/2C agonist, 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI) to augment ventral pallidal cell firing also was enhanced in METH‐sensitized rats. These data reveal that METH‐induced behavioral sensitization renders the VP more responsive to METH and is associated with a functional upregulation of 5‐HT 2 receptors. Synapse 62:14–21, 2008. © 2007 Wiley‐Liss, Inc.