Neonatal 6-hydroxydopamine-induced dopamine depletions: Motor activity and performance in maze learning

Archer, Trevor; Danysz, Wojciech; Fredriksson, Anders; Jonsson, Gösta; Luthman, Johan; Sundström, Eric; Teiling, Anna

doi:10.1016/0091-3057(88)90358-9

Cited by 76 publications

(30 citation statements)

References 17 publications

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“…Some studies evaluate both cognitive and motor function of DA-depleted rats after intracerebral neonatal microinjections of 6-hydroxydopamine (6-OHDA). This experimental model, in developing rats, is strikingly similar to the clinical syndrome of MBD (Shaywitz et al 1976;Archer et al 1988). Animal models provide us with important findings in order to understand the anatomic bases of motor learning and motor control.…”

Section: Animal Models and The ''Network Inhibition Hypothesis'' Of Nmentioning

confidence: 53%

Pathophysiology of NSS in ADHD

Pasini

D’Agati

2009

The World Journal of Biological Psychiatry

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Attention deficit/hyperactivity disorder (ADHD) is the behavioural disorder most commonly diagnosed in childhood. In addition to the main symptoms of inattention, impulsiveness and hyperactivity, neurological soft signs (NSS) are often associated with ADHD. NSS are discrete motor and sensory disorders that cannot be linked to specific cerebral lesions. We review all the scientific contributions on NSS in ADHD. The conclusions support the presence of an alteration in the neural networks for motor control inhibition, at the base of the pathophysiology of NSS in children with ADHD, as well as a possible central role of dopamine in these neural circuits.

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Section: Animal Models and The ''Network Inhibition Hypothesis'' Of Nmentioning

confidence: 53%

Pathophysiology of NSS in ADHD

Pasini

D’Agati

2009

The World Journal of Biological Psychiatry

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“…Lesioning of dopaminergic systems by ICV injection of 6-OHDA or MPTP also causes both catalepsia and bradykinesia in adult rats and monkeys Stricker, 1973, Deumens et al, 2002). These studies along with the current data suggest an essential role for dopaminergic innervation in locomotor activity (Zigmond and Stricker, 1973, Archer et al, 1988, Deumens et al, 2002. Serotonin also has been implicated in locomotion (Geyer, 1996, Jacobs andFornal, 1997).…”

Section: Discussionmentioning

confidence: 91%

“…This finding contradicts data from other studies. Other investigators have shown that 6-OHDA-treated rats exhibit a retarded acquisition of running responses to acquire food pellets in a modified version of the Olton radial arm maze (Archer et al, 1988). Furthermore, 6-OHDA-treated rats also have been shown to be drastically impaired in the swim maze task compared with controls (Archer et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

“…Dopaminergic lesioning via 6-OHDA treatment have been shown to cause locomotor defects in a number of animal models. Neonatal ICV 6-OHDA infusion causes considerable and long-lasting locomotor activity in juvenile and adult rats (Shaywitz et al, 1976, Miller et al, 1981, Archer et al, 1988. Lesioning of dopaminergic systems by ICV injection of 6-OHDA or MPTP also causes both catalepsia and bradykinesia in adult rats and monkeys Stricker, 1973, Deumens et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Neonatal 6-hydroxydopamine lesions of the frontal cortex in rats: Persisting effects on locomotor activity, learning and nicotine self-administration

et al. 2008

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Dopaminergic innervation of the frontal cortex in adults is important for a variety of cognitive functions and behavioral control. However, the role of frontal cortical dopaminergic innervation for neurobehavioral development has received little attention. In the current study, rats were given dopaminergic lesions in the frontal cortex with local micro-infusions of 6-hydroxydopamine (6-OHDA) at one week of age. The long-term behavioral effects of neonatal frontal cortical 6-OHDA lesions were assessed in a series of tests of locomotor activity, spatial learning and memory, and intravenous (IV) nicotine self-administration. In addition, neurochemical indices were assessed with tissue homogenization and HPLC in the frontal cortex, striatum, and nucleus accumbens of neonatal and adult rats after neonatal 6-OHDA lesions. In neonatal rats, frontal 6-OHDA lesions as intended caused a significant reduction in frontal cortical dopamine without effects on frontal cortical serotonin and norepinephrine. The frontal cortical dopamine depletion increased serotonin and norepinephrine levels in the nucleus accumbens. Locomotor activity assessment during adulthood in the Figure-8 maze showed that lesioned male rats were hyperactive relative to sham lesioned males. Locomotor activity of female rats was not significantly affected by the neonatal frontal 6-OHDA lesion. Learning and memory in the radial-arm maze was also affected by neonatal frontal 6-OHDA lesions. There was a general trend toward impaired performance in early maze acquisition and a paradoxical improvement at the end of cognitive testing. Nicotine self-administration showed significant lesion × sex interactions. The sex difference in nicotine self-administration with females self-administering significantly more nicotine than males was reversed by neonatal 6-OHDA frontal cortical lesions. Neurochemical studies in adult rats showed that frontal cortical dopamine and DOPAC levels significantly correlated with nicotine self-administration in the 6-OHDA lesioned animals but not in the controls. Frontal cortical serotonin and 5HIAA showed inverse correlations with nicotine self-administration in the 6-OHDA lesioned animals but not in the controls. These results show that interfering with normal dopamine innervation of the frontal cortex during early postnatal development has persisting behavioral effects, which are sex-specific.

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“…The loss of the DAdependent decrease in synaptic efficacy in vivo could lead to disturbances of striatal and basal ganglia function, and consequently produce changes in motor and cognitive function. Changes in motor function and learning have been observed in both neonatal 6-OHDA-treated rats and D2KO mice, although the phenotypes differ between these rodent models (43)(44)(45)(46)(47)(48).…”

Section: Involvement Of Mechanisms Downstream From Presynaptic Neuronalmentioning

confidence: 99%

Dopamine-dependent synaptic plasticity in striatum during in vivo development

Tang¹

2001

Proceedings of the National Academy of Sciences

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The neurotransmitters dopamine (DA) and glutamate in the striatum play key roles in movement and cognition, and they are implicated in disorders of the basal ganglia such as Parkinson's disease. Excitatory synapses in striatum undergo a form of developmental plasticity characterized by a decrease in glutamate release probability. Here we demonstrate that this form of synaptic plasticity is DA and DA D2 receptor dependent. Analysis of spontaneous synaptic responses indicates that a presynaptic mechanism involving inhibition of neurotransmitter release underlies the developmental plasticity. We suggest that a major role of DA in the striatum is to initiate mechanisms that regulate the efficacy of excitatory striatal synapses, producing a decrease in glutamate release. The striatum is the point of entry of information into the basal ganglia, and it has important roles in motor control and habit learning (1, 2). The neocortex (3, 4) and thalamus (5) provide the major excitatory inputs to striatal medium spiny projection neurons (MSNs). Morphological studies have demonstrated that the majority of these afferent terminals impinge on the head of the spines on the dendrites of striatal MSNs (6, 7), whereas most dopaminergic afferent fibers coming from the substantia nigra make synapses on the necks of the same dendritic spines (8). This close anatomical localization of these two types of synapses suggests that dopamine (DA) released from the nigrostriatal afferent terminals may have modulatory effects on the excitatory signals generated from the cortex and thalamus (9).The importance of DA in normal striatal function is evidenced by the severe disruption of behavior observed in Parkinson's disease and after chemical lesions of nigral dopaminergic inputs to striatum (10). In fact, DA plays a variety of important physiological roles in striatum (11-15). However, the cellular physiological actions of DA that contribute to striatal function in vivo are not fully understood. In the present study, we wanted to examine the role of the DA system in plasticity of synaptic efficacy at striatal glutamatergic synapses during early postnatal development.Long-term changes in synaptic efficacy have been postulated to be cellular mechanisms underlying learning and memory (16). Synaptic plasticity of this type may also be involved in maturation of central synapses. One form of synaptic plasticity that may play an important role in maturation of excitatory synapses in the striatum is a decrease in the efficacy of transmission that takes place during weeks 2-3 of postnatal development (17,18). This decrease in efficacy appears to involve a decrease in glutamate release. However, little is known about the role of different striatal neurotransmitters in this developmental plasticity.To determine whether DA plays a role in the synaptic plasticity during maturation of excitatory striatal synapses we examined synaptic transmission at glutamatergic synapses in two animal models over the period from postnatal day (PD) 12 to PD29. One model was a...

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Neonatal 6-hydroxydopamine-induced dopamine depletions: Motor activity and performance in maze learning

Cited by 76 publications

References 17 publications

Pathophysiology of NSS in ADHD

Pathophysiology of NSS in ADHD

Neonatal 6-hydroxydopamine lesions of the frontal cortex in rats: Persisting effects on locomotor activity, learning and nicotine self-administration

Dopamine-dependent synaptic plasticity in striatum during in vivo development

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