title: Social isolation rearing increases dopamine uptake and psychostimulant potency in the striatum.
abstract: Social isolation rearing (SI) is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like behaviors. These animals also exhibit an increased propensity to administer psychostimulants, such as cocaine; however, the mechanisms governing this increased addiction vulnerability remain to be elucidated. Long-term stressors have been shown to produce important alterations in nucleus accumbens core (NAc) function. The NAc regulates motivated and goal-directed behaviors, and individual differences in NAc function have been shown to be predictive of addiction vulnerability. Rats were reared in group (GH; 4/cage) or SI (1/cage) conditions from weaning (PD 28) into early adulthood (PD 77) and dopamine release was assessed using voltammetry in brain slices containing the NAc and dorsomedial striatum. SI rats exhibited enhanced dopamine release and uptake in both regions compared to GH rats. In regard to psychostimulant effects directly at the dopamine transporter (DAT), methylphenidate and amphetamine, but not cocaine, inhibited uptake more in SI than GH rats. The increased potencies were positively correlated with uptake rates, suggesting that increased potencies of amphetamine-like compounds are due to changes in DAT function. Cocaine's effects on uptake were similar between rearing conditions, however, cocaine enhanced evoked dopamine release greater in SI than GH rats, suggesting that the enhanced cocaine reinforcement in SI animals involves a DAT independent mechanism. Together, the results provide the first evidence that greater psychostimulant effects in SI compared to GH rats are due to effects on dopamine terminals related to uptake dependent and independent mechanisms.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: yorgason@ohsu.edu.
authors.forename: Jordan T
authors.initials: JT
authors.lastname: Yorgason
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: erin.calipari@mssm.edu.
authors.forename: Erin S
authors.initials: ES
authors.lastname: Calipari
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: mferris@wakehealth.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ferris
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: akarkhan@wakehealth.edu.
authors.forename: Anushree N
authors.initials: AN
authors.lastname: Karkhanis
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: sfordahl@wakehealth.edu.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Fordahl
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: jweiner@wakehealth.edu.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Weiner
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, United States. Electronic address: srjones@wakehealth.edu.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Jones
mesh_terms: D000367:Age Factors; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012934:Social Isolation
chemical_list: D000697:Central Nervous System Stimulants; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008774:Methylphenidate; D000661:Amphetamine; D003042:Cocaine; D004298:Dopamine
keywords: Accumbens; Dopamine; Early life stress; Psychostimulant; Striatum; Voltammetry