title: Differential regulation of 5-HT2A receptor mRNA expression following withdrawal from a chronic escalating dose regimen of D-amphetamine.
abstract: Several lines of evidence indicate that psychostimulant withdrawal can induce negative emotional symptoms, such as anhedonia and dysphoria, which may be due in part, to dysfunction of the serotonin (5-HT) system, including alterations in 5-HT receptors. For example, changes in 5-HT(2A) receptor function in prefrontal cortex (PFC) have been reported in association with psychostimulant withdrawal. However, it is not known if alterations in 5-HT(2A) receptor mRNA expression occur in the PFC or other limbic-associated areas following withdrawal from chronic psychostimulant treatment. The goal of the current study was to determine the effects of chronic, escalating doses of D-amphetamine (D-AMPH) and withdrawal on the expression of 5-HT(2A) receptors in the cortex, caudate putamen, NAc and hippocampus of rat brain. Animals were treated three times a day for 4 days with escalating doses of D-AMPH (1-10 mg/kg). Twenty-four hours after the final dose of D-AMPH, animals were sacrificed and the tissue processed for in situ hybridization histochemistry. Chronic, escalating doses of D-AMPH, followed by a 24 h withdrawal period, significantly decreased 5-HT(2A) receptor mRNA expression in the prefrontal, motor and cingulate cortices, while 5-HT(2A) receptor mRNA expression in the NAc, caudal CPu and hippocampus were significantly increased. These data indicate that region-specific changes in 5-HT(2A) receptor mRNA expression occur in limbic system and associated areas following chronic D-AMPH treatment, supporting the notion that alterations in the 5-HT system may contribute to the negative emotional aspects of psychostimulant withdrawal.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St. Macon, GA 31207, USA. horner_ka@mercer.edu
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Horner
authors.forename: Yamiece E
authors.initials: YE
authors.lastname: Gilbert
authors.forename: Erika S
authors.initials: ES
authors.lastname: Noble
mesh_terms: D000818:Animals; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000009:adverse effects*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D003913:Dextroamphetamine