Methamphetamine-induced sensitization includes a functional upregulation of ventral pallidal 5-HT2A/2C receptors.
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-HT2A/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-HT2A/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-HT2 receptors.
Napier
T Celeste
TC
Department of Pharmacology, Rush University Medical Center, Chicago, Illinois 60612, USA. celeste_napier@rush.edu
Istre
Erik D
ED
D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004594:Electrophysiology; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015854:Up-Regulation
D000697:Central Nervous System Stimulants; D044348:Receptors, Serotonin, 5-HT2; D017366:Serotonin Receptor Agonists; D008694:Methamphetamine