Apparent sprouting of striatal serotonergic terminals after dopamine-depleting brain lesions in neonatal rats

doi:10.1016/0006-8993(84)90665-6

Brain Research

Volume 291, Issue 1, 16 January 1984, Pages 164-167

https://doi.org/10.1016/0006-8993(84)90665-6 Get rights and content

Abstract

Near-total dopamine-depleting brain lesions produced in 3-day-old rats by intracerebroventricular injection of the neurotoxin 6-hydroxydopamine led to pronounced increases in striatal serotonin (5-HT) and 5-hydroxyindoleacetic acid contents 1–8 months later. This effect was associated with an increase in in vitro high affinity 5-HT uptake, suggesting that proliferation of new serotonergic terminals had occurred within the striatum. No such effect was obtained when comparable brain lessions were produced in adult rats.

References (18)

Bjo¨rklundA. et al.
Mechanisms of regrowth of the bulbospinal serotonin system following 5,6-dihydroxytryptamine induced axotomy. I. Biochemical correlates
Brain Research
(1980)
DaviesJ. et al.
Neuropharmacological studies on the nigro-striatal and raphe-striatal system in the rat
Europ. J. Pharmacol.
(1978)
JonssonG.
Developmental characteristics of central monoamine neurons and their reciprocal relation
Exp. Neurol.
(1976)
PickelV.M. et al.
Proliferation of norepinephrine-containing axons in rat cerebellar cortex after peduncle lesions
Brain Research
(1973)
RaismanG. et al.
A quantitative investigation of the development of collateral reinnervation after partial deafferentation of the septal nuclei
Brain Research
(1973)
SteneviU. et al.
Growth of intact central adrenergic axons in the denervated lateral geniculate body
Exp. Neurol.
(1972)
TassinJ.P. et al.
Collateral sprouting and reduced activity of the rat mesocortical dopaminergic neurons after selective destruction of the ascending noradrenergic bundles
Neuroscience
(1979)
TernauxJ.P. et al.
The topographical distribution of serotoninergic terminals in the neostriatum of the rat and the caudate nucleus of the cat
Brain Research
(1977)
Bjo¨rklundA. et al.
Regeneration and plasticity of central serotoninergic neurons: a review
J. Physiol. (Paris)
(1981)

There are more references available in the full text version of this article.

Cited by (224)

Enhancing the resolution of behavioral measures: Key observations during a forty year career in behavioral neuroscience
2023, Neuroscience and Biobehavioral Reviews
This manuscript reviews several key observations from the research program of Professor John P. Bruno that are believed to have significantly advanced our understanding of the brain’s mediation of behavior. This review focuses on findings within several important research areas in behavioral neuroscience, including a) age-dependent neurobehavioral plasticity following brain damage; b) the role of the cortical cholinergic system in attentional processing and cognitive flexibility; and c) the design and validation of animal models of cognitive deficits in schizophrenia. In selecting these observations, emphasis was given to examples in which the heuristic potency was increased by maximizing the resolution and microanalysis of behavioral assays in the same fashion as one typically refines neuronal manipulations. Professor Bruno served the International Behavioral Neuroscience Society (IBNS) as an IBNS Fellow (1995-present) and President of the IBNS (2001–02).
Compensatory neuritogenesis of serotonergic afferents within the striatum of a transgenic rat model of Parkinson's disease
2020, Brain Research
The majority of patients with Parkinson’s disease (PD) suffer from L-DOPA-induced dyskinesia (LID). Besides a dysfunctional dopaminergic system, changes of the serotonergic network may be linked to this severe and adverse symptom. Particularly, serotonergic neurons have the potential to synthesize dopamine, likely associated with a disproportional dopamine release within the striatum. We hypothesized that the serotonergic system is adaptively altered in the striatum due to the reduced dopaminergic input. To answer this question, we analyzed a transgenic rat PD model ubiquitously expressing human α-synuclein using a bacterial artificial chromosome. Neurite analysis showed a profound loss of dopaminergic fibers by ~30–40% within the dorsal striatum paralleled by a ~50% reduction of dopaminergic neurons in the substantia nigra pars compacta. In contrast, serotonergic fibers showed an increased fiber density in the dorsal striatum by ~100%, while the number of serotonergic neurons within the raphe nuclei (RN) and its proximal neuritic processes were unaffected. Furthermore, both the dopaminergic and serotonergic fiber density remained unchanged in the neighboring motor cortex M1/M2. Interestingly, essential enzymes required for L-DOPA turnover and dopamine release were expressed in serotonergic neurons of the RN. In parallel, the serotonergic autoreceptor levels involved in a serotonergic negative feedback loop were reduced within the striatum, suggesting a dysfunctional neurotransmitter release. Overall, the increased serotonergic fiber density with its capacity for dopamine release within the striatum suggests a compensatory, site-specific serotonergic neuritogenesis. This maladaptive serotonergic plasticity may be linked to adverse symptoms such as LIDs in PD.
Neurobehavioral changes arising from early life dopamine signaling perturbations
2020, Neurochemistry International
Dopamine (DA) signaling is critical to the modulation of multiple brain functions including locomotion, reinforcement, attention and cognition. The literature provides strong evidence that altered DA availability and actions can impact normal neurodevelopment, with both early and enduring consequences on anatomy, physiology and behavior. An appreciation for the developmental contributions of DA signaling to brain development is needed to guide efforts to preclude and remedy neurobehavioral disorders, such as attention-deficit/hyperactivity disorder, addiction, bipolar disorder, schizophrenia and autism spectrum disorder, each of which exhibits links to DA via genetic, cellular and/or pharmacological findings. In this review, we highlight research pursued in preclinical models that use genetic and pharmacological approaches to manipulate DA signaling at sensitive developmental stages, leading to changes at molecular, circuit and/or behavioral levels. We discuss how these alterations can be aligned with traits displayed by neuropsychiatric diseases. Lastly, we review human studies that evaluate contributions of developmental perturbations of DA systems to increased risk for neuropsychiatric disorders.
Striatal circuit development and synapse maturation
2020, Synapse Development and Maturation: Comprehensive Developmental Neuroscience
The basal ganglia are a series of subcortical nuclei essential for goal-directed motor actions and reward-based behavior in vertebrates. The goal of this chapter is to review the development of the striatum which is the largest nucleus and the main point of entry to the multiple afferent systems that are integrated and processed by the basal ganglia. We start describing early striatal patterning during embryonic development and continue through key stages of maturation after birth, including the compartmentalization of striatal circuits, maturation of cellular properties, assembly of synapses, and the maturation of striatal patterns of activity.
Characterization of nociceptive response to chemical, mechanical, and thermal stimuli in adolescent rats with neonatal dopamine depletion
2015, Neuroscience
Rats with dopamine depletion caused by 6-hydroxydopamine (6-OHDA) treatment during adulthood and the neonatal period exhibit akinetic motor activity and spontaneous motor hyperactivity during adolescence, respectively, indicating that the behavioral effects of dopamine depletion depend on the period of lesion development. Dopamine depletion during adulthood induces hyperalgesic response to mechanical, thermal, and/or chemical stimuli, whereas the effects of neonatal dopamine depletion on nociceptive response in adolescent rats are yet to be examined. The latter aspect was addressed in this study, and behavioral responses were examined using von-Frey, tail flick, and formalin tests. The formalin test revealed that rats with neonatal dopamine depletion exhibited a significant increase in nociceptive response during interphase (6–15 min post formalin injection) and phase 2 (16–75 min post formalin injection). This increase in nociceptive response to the formalin injection was not reversed by pretreatment with methamphetamine, which ameliorates motor hyperactivity observed in adolescent rats with neonatal 6-OHDA treatment. The von-Frey filament and tail flick tests failed to reveal significant differences in withdrawal thresholds between neonatal 6-OHDA-treated and vehicle-treated rats. The spinal neuronal response to the formalin injection into the rat hind paw was also examined through immunohistochemical analysis of c-Fos protein. Significantly increased numbers of c-Fos-immunoreactive cells were observed in laminae I–II and V–VI of the ipsilateral spinal cord to the site of the formalin injection in rats with neonatal dopamine depletion compared with vehicle-treated rats. These results suggest that the dopaminergic neural system plays a crucial role in the development of a neural network for tonic pain, including the spinal neural circuit for nociceptive transmission, and that the mechanism underlying hyperalgesia to tonic pain is not always consistent with that of spontaneous motor hyperactivity induced by neonatal dopamine depletion.
Does serotonin deficit mediate susceptibility to ADHD?
2015, Neurochemistry International
Citation Excerpt :
Drugs like AMPH and MPH can reduce hyperactivity in 6-OHDA lesioned rat (Archer et al., 2002; Heffner and Seiden, 1982) so this model has ‘predictive validity’. Though the primary target of this model was the DA system, discernable changes in 5-HT system were also reported (Avale et al., 2004; Bruno et al., 1987; Brus et al., 2004; Luthman et al., 1990; Snyder et al., 1986; Stachowiak et al., 1984; Zhang et al., 2002). Tissue concentration of 5-HT and its metabolites, 5-HTT density, number 5-HT neurons, K+ stimulated 5-HT release is increased in striatum of 6-OHDA lesioned rats (Avale et al., 2004; Bruno et al., 1987; Luthman et al., 1990, 1997; Snyder et al., 1986; Stachowiak et al., 1984; Zhang et al., 2002).
The onset of attention-deficit-hyperactivity-disorder (ADHD) in childhood is characterized by developmentally inappropriate levels of hyperactivity, impulsivity and inattention. A chronic deficit of serotonin (5-HT) at the synapse may trigger symptoms of ADHD. This review focuses on neuro-anatomical, experimental and clinical pharmacological evidence, as well as the genetic underpinnings of serotoninergic involvement in the etiology of ADHD. Neuro-anatomical investigations suggest that serotonin through the orbitofrontal–striatal circuitry may regulate behavioral domains of hyperactivity and impulsivity in ADHD. Studies from animal models of ADHD indicate intimate interplay between 5-HT and dopaminergic neurotransmission. Selective serotonin re-uptake inhibitors, as also non-stimulant drugs acting on the 5-HT system are, however, clinically effective. They impart less severe side effects in patients with no risk of addiction. Oral administration of l-tryptophan, the amino acid precursor of 5-HT, significantly alleviates ADHD symptoms. Given the multifactorial nature of ADHD, candidate gene and genome-wide association studies have suggested that serotoninergic gene variants are associated with increased risk of ADHD with each locus individually exerting a modest effect on overall risk.

View all citing articles on Scopus

View full text

Apparent sprouting of striatal serotonergic terminals after dopamine-depleting brain lesions in neonatal rats

Abstract

Brain Research

Europ. J. Pharmacol.

Exp. Neurol.

Brain Research

Brain Research

Exp. Neurol.

Neuroscience

Brain Research

Regeneration and plasticity of central serotoninergic neurons: a review

J. Physiol. (Paris)