Developmental Brain Research 137 (2002) 135–138 www.elsevier.com / locate / bres Short communication Serotonin transporter binding increases in caudate-putamen and nucleus accumbens after neonatal 6-hydroxydopamine lesions in rats: implications for motor hyperactivity a,b, b b b * Kehong Zhang , Eugen Davids , Frank I. Tarazi , Ross J. Baldessarini a Mailman Research Center, McLean Division of Massachusetts General Hospital, 115 Mill Street, Belmont, MA 02478, USA b Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA 02115, USA Accepted 6 June 2002 Abstract We examined serotonin (5-HT) transporters in rat forebrain using quantitative autoradiography at three distinct developmental stages after neonatal 6-hydroxydopamine lesions. The lesions substantially increased 5-HT transporter binding in both caudate-putamen and nucleus accumbens, but not cerebral cortex. The effects reached maximal levels as early as postnatal day (PD) 24, and were sustained until early adulthood. Behavioral analyses indicated that neonatal lesions resulted in motor hyperactivity on PD 24, but not on PD 36 or 59. These findings suggest that excess 5-HT transporters reflect serotonin hyperinnervation reported to occur in lesioned rats, and may modulate motor hyperactivity.  2002 Elsevier Science B.V. All rights reserved. Theme: Neural basis of behavior Topic: Monoamines and behavior Keywords: Motor hyperactivity; 6-Hydroxydopamine; 5-Hydroxytryptamine (5-HT) transporter; Caudate-putamen; Nucleus accumbens; Development Behavioral effects of selective lesions of central dopa- that also differ from responses to such lesions in adult- mine (DA) neurons with the neurotoxin 6-hydroxy- hood. Particularly prominent among changes after neonatal dopamine (6-OHDA) are largely dependent on the time of lesions is hyperinnervation of neostriatum by serotonin lesioning [14]. In adult rats, extensive DA lesions result in (5-hydroxytryptamine, 5-HT) containing neurons [16,26]. behavioral deficits characteristic of Parkinson’s disease The functional significance of this response, and par- [29]. After neonatal 6-OHDA lesioning, rats do not display ticularly its relationship to the complex behavioral conse- gross deficits in motor functioning [24,31]. Instead, they quences of neonatal lesions, remain obscure, in part due to exhibit temporary, age-limited, spontaneous motor hy- the following reasons. peractivity [19,23] that can be dose-dependently reversed First, neonatal 6-OHDA lesions may lead to several by psychostimulant drugs such as methylphenidate behavioral deficits in addition to motor hyperactivity. Such [8,18,32]. These features closely resemble the hyperactivi- effects include self-mutilatory behavior [3], oral ty in patients with attention deficit hyperactivity disorder dyskinesias [9] and deficits in learning and memory [27]. (ADHD) and therapeutic effects of psychostimulants [1]. Which behaviors emerge after lesioning is highly depen- As a result, rats with neonatal 6-OHDA lesions are widely dent upon the lesioning procedure, including the timing used as a laboratory model for ADHD. and the route of 6-OHDA administration, as well as the Neonatal 6-OHDA lesions induce neuronal adaptations age at which behavioral assessment is carried out. Exam- ples for such variation include failure to induce self- mutilatory behavior using neonatal intracisternal 6-OHDA *Corresponding author. Tel.: 11-617-855-3222; fax: 11-617-855- administration [11] and our failure to induce motor hy- 3479. E-mail address: kz@mclean.harvard.edu (K. Zhang). peractivity with neonatal intracerebroventricular injection 0165-3806 / 02 / $ – see front matter  2002 Elsevier Science B.V. All rights reserved. PII: S0165-3806(02)00436-4