title: Effects of chronic environmental and social stimuli during adolescence on mesolimbic dopaminergic circuitry markers.
abstract: Previously, we have shown that chronic exposure to environmental and social stimuli (ESS) during adolescence prevents the development of behavioral sensitization to amphetamine in adult rats. At the onset of the peripubertal-juvenile period (28-d) male rats were subjected to a 28-d long intermittent ESS protocol or handled as controls (NO-ESS). Twenty-four hours after the last session of ESS or NO-ESS, all rats started a regimen of behavioral sensitization to amphetamine (1mg/kg, i.p.), in which rats were injected every third day with amphetamine or saline on four occasions. Then following one week abstinence all rats were challenged with a lower dose of amphetamine (0.5mg/kg, i.p.) and their locomotor activity monitored for 2h. Our results showed that while NO-ESS rats developed behavioral sensitization to amphetamine, ESS rats did not develop this behavior. All rats were then sacrificed 3 days following the challenge to allow for amphetamine clearance. Since mesolimbic dopamine has been implicated in behavioral sensitization to amphetamine we compared messenger RNA (mRNA) expression of key dopamine-related molecules in the mesolimbic circuitry in ESS and NO-ESS rats. A decrease in dopaminergic D1 receptor (D1R) gene expression in the caudate-putamen (CPu) was associated with amphetamine sensitization in the controls, possibly as a result of a chronic increase in DA release. In contrast, amphetamine treatment did not modulate D1R mRNA levels in ESS rats. No change has been detected in any other dopaminergic markers [D2R, D3R, tyrosine hydroxylase (TH) or dopamine transporter (DAT) mRNAs]. Consequently, we conclude that ESS may inhibit the development of behavioral sensitization to amphetamine through preventing the decrease in CPu D1R mRNA levels.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee 4300, FL 32306, USA. Mohamed.Kabbaj@Med.FSU.edu
authors.forename: M
authors.initials: M
authors.lastname: Kabbaj
authors.forename: C
authors.initials: C
authors.lastname: Isgor
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004777:Environment; D017403:In Situ Hybridization; D008032:Limbic System / Q000254:growth & development / Q000502:physiology*; D008297:Male; D009415:Nerve Net / Q000254:growth & development / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012931:Social Environment; D016707:Tissue Fixation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D014446:Tyrosine 3-Monooxygenase; D003913:Dextroamphetamine; D004298:Dopamine