Mesocorticolimbic dopaminergic network: functional and regulatory roles

Moal, Michel Le; Simon, H.

doi:10.1152/physrev.1991.71.1.155

Cited by 1,037 publications

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“…Recovery of DAT binding in NAc was temporally paralleled by normalization of motor behavior with maturation. The mesolimbic DA pathway to NAc plays an important role in exploratory behavior (Le Moal and Simon 1991), including in 6-OHDA lesion-induced hyperactivity (Heffner et al 1983). Therefore, it is possible that postlesioning plasticity involving DA neurotransmission in NAc may contribute to normalization of motor activity in early adulthood.…”

Section: Discussionmentioning

confidence: 99%

Plasticity of Dopamine D4 Receptors in Rat Forebrain Temporal Association with Motor Hyperactivity Following Neonatal 6-Hydroxydopamine Lesioning

Zhang

Tarazi

Davids

et al. 2002

Neuropsychopharmacology

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Genetic studies suggest that dopamine D 4 receptor polymorphism is associated with attention deficit hyperactivity disorder (ADHD). We recently reported that motor hyperactivity in juvenile male rats with neonatal 6-hydroxydopamine lesions of the central dopamine system canAttention-deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition characterized by hyperactivity, inattention and impulsivity, typically in school-aged boys (Barkley 1990). Abnormal dopamine (DA) neurotransmission has long been considered to underlie the disorder since most symptoms of ADHD can be alleviated by psychostimulant drugs, notably methylphenidate and amphetamines, that release DA among other actions. Increased radioligand binding to dopamine transporters (DAT) in patients with ADHD identified in recent brain imaging studies further implicates deficient DA functioning in the disorder (Dougherty et al. 1999;Dresel et al. 2000).DA modulates physiological processes through activation of five G-protein NO . 5 ADHD by genetic linkage studies (La Hoste et al. 1996). Human D 4 receptors occur in multiple forms with 2-11 copies of a 16-amino acid sequence in the putative third intracellular loop of the peptide (Van Tol et al. 1992;Lichter et al. 1993;Asghari et al. 1994). One such allele is the D 4.7 receptor, containing seven repeats of this sequence. It has repeatedly been associated with ADHD, as well as related behavioral traits such as novelty-seeking and impulsivity (Benjamin et al. 1996;Ebstein et al. 1996;La Hoste et al. 1996;Bailey et al. 1997;Rowe et al. 1998;Swanson et al. 1998;Faraone et al. 1999;Barr et al. 2000).Some features of ADHD are simulated in several laboratory models, including: (1) rats with neonatal lesions of the central DA system induced by the neurotoxin 6-hydroxydopamine (6-OHDA; Shaywitz et al. 1976); (2) the spontaneously hypertensive Kyoto-Wistar rat (Tucker and Johnson 1981); (3) nonhuman primates treated with the DA neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; Roeltgen and Schneider 1991); and (4) genetic knock-out mice lacking functional DAT (Giros et al. 1996). Juvenile male rats with neonatal 6-OHDA lesions are a particularly appropriate model for the hyperactivity of ADHD in that lesion-induced motor hyperactivity is most prominent at an age corresponding to human periadolescence (Shaywitz et al. 1976;Erinoff et al. 1979), and is dose-dependently antagonized by stimulants used to treat clinical ADHD (Heffner and Seiden 1982). In addition, the model is associated with learning deficits that are also antagonized by stimulants (Takasuna and Iwasaki 1996;Wool et al. 1987).We found recently that motor hyperactivity following 6-OHDA lesioning of neonatal rats can be reversed dose-dependently by selective antagonists for D 4 but not D 2 receptors, and exacerbated by a D 4 agonist (Zhang et al. 2001b). In addition, motor hyperactivity correlated closely with the magnitude of increased D 4 , but not D 2 receptor binding in basal forebrain. The present study further inv...

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Section: Discussionmentioning

confidence: 99%

Plasticity of Dopamine D4 Receptors in Rat Forebrain Temporal Association with Motor Hyperactivity Following Neonatal 6-Hydroxydopamine Lesioning

Zhang

Tarazi

Davids

et al. 2002

Neuropsychopharmacology

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“…This DA pathway plays an important role in locomotor activity, emotion, motivation and working memory. 7,8 In addition to the mesocortical/mesolimbic DA pathway there is accumulating evidence for a role of glutamate and N-methyl-D-aspartate (NMDA) glutamate receptors in schizophrenia. 9 Glutamate and DA, which share common postsynaptic targets, are believed to interact in a reciprocal manner at both cortical and subcortical structures.…”

Section: Introductionmentioning

confidence: 99%

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

et al. 2007

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The transcription factor Nurr1 (NR4A2) has been found to play a critical role in the development of midbrain dopaminergic neurons. Nurr1 heterozygous ( þ /À) male and female mice expressing 35-40% of normal levels of Nurr1 were generated and examined in animal models related to symptoms of schizophrenia. The Nurr1 ( þ /À) mice displayed hyperactivity in a novel environment, which persisted after administration of the dopamine-mimetic amphetamine and the N-methyl-D-aspartate receptor antagonist phencyclidine. The Nurr1 ( þ /À) mice were deficient in the retention of emotional memory and showed an enhanced response to swim stress. In addition, Nurr1 ( þ /À) male mice displayed a reduced dopamine turnover in the striatum and an enhanced dopamine turnover in the prefrontal cortex, while female mice showed an opposite pattern. These results show that Nurr1 ( þ /À) mice display a pattern of behaviors indicative of potential relevance for symptoms of schizophrenia combined with a gender-specific abnormal dopamine transmission in the striatum and prefrontal cortex, respectively. This suggests that the Nurr1 mutant mouse may be a potential animal model for studies on some of the behavioral and molecular mechanisms underlying schizophrenia.

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“…Dopamine (DA) is a neurotransmitter related to complex behaviors, such as: reward perception, social interaction [1,2], and is also linked to memory consolidation both in humans and rodents [3]. Alterations in DA synaptic regulation are related to a large variety of mental diseases, such as schizophrenia, hyperactivity, mood disorders, and Parkinson disease [4,5].…”

Section: H I G H L I G H T Smentioning

confidence: 99%

“…The results indicate that a mild enhancement of dopaminergic levels can be detrimental to object recognition, and that this deficit can be rescued by a low dose of a D2 dopamine receptor antagonist. This suggests that novel object recognition is optimal at intermediate levels of D2 receptor activity.© 2016 Elsevier B.V. All rights reserved.Dopamine (DA) is a neurotransmitter related to complex behaviors, such as: reward perception, social interaction [1,2], and is also linked to memory consolidation both in humans and rodents [3]. Alterations in DA synaptic regulation are related to a large variety of mental diseases, such as schizophrenia, hyperactivity, mood disorders, and Parkinson disease [4,5].…”

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confidence: 99%

Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice

França

Muratori

Nascimento

et al. 2016

Behavioural Brain Research

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h i g h l i g h t s• Heterozygous mice for dopamine transporter (DAT+/−) exhibit higher levels of synaptic dopamine.• Here we confirmed that D2 antagonism can interfere in object recognition.• We observed in DAT+/− a natural phenotype of impaired novel object memory recognition.• The injection of haloperidol at 0.05 mg before object exposition restored object recognition.• This effect could be explained by restoring D2 activity to optimal levels, acting on memory acquisition. a r t i c l e i n f o Genetically-modified mice without the dopamine transporter (DAT) are hyperdopaminergic, and serve as models for studies of addiction, mania and hyperactive disorders. Here we investigated the capacity for object recognition in mildly hyperdopaminergic mice heterozygous for DAT (DAT +/−), with synaptic dopaminergic levels situated between those shown by DAT −/− homozygous and wild-type (WT) mice. We used a classical dopamine D2 antagonist, haloperidol, to modulate the levels of dopaminergic transmission in a dose-dependent manner, before or after exploring novel objects. In comparison with WT mice, DAT +/− mice showed a deficit in object recognition upon subsequent testing 24 h later. This deficit was compensated by a single 0.05 mg/kg haloperidol injection 30 min before training. In all mice, a 0.3 mg/kg haloperidol injected immediately after training impaired object recognition. The results indicate that a mild enhancement of dopaminergic levels can be detrimental to object recognition, and that this deficit can be rescued by a low dose of a D2 dopamine receptor antagonist. This suggests that novel object recognition is optimal at intermediate levels of D2 receptor activity.© 2016 Elsevier B.V. All rights reserved.Dopamine (DA) is a neurotransmitter related to complex behaviors, such as: reward perception, social interaction [1,2], and is also linked to memory consolidation both in humans and rodents [3]. Alterations in DA synaptic regulation are related to a large variety of mental diseases, such as schizophrenia, hyperactivity, mood disorders, and Parkinson disease [4,5]. * Corresponding author.E-mail addresses: brunolobaosoares@gmail.com, brunolobaosoares@hotmail.com (B. Lobão-Soares).DA has many receptor subtypes, but they are basically divided in D1 and D2 families [3]. DA, mainly through D1 receptors, elicits the onset of the late phase of long term potentiation in the hippocampus [6], control plasticity-induced protein synthesis [6], and enhance the persistence of hippocampus-dependent memories [7].The involvement of both dopamine receptors families with learning and memory is widely reported for working memory [3], spatial learning [3,6], aversive memory [7], reward-related learning [8] and cognitive flexibility [9]. In particular, impairment in object recognition has been induced by D2 activity suppression due to haloperidol IP injection [10], by D1 activity suppression trough http://dx

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Mesocorticolimbic dopaminergic network: functional and regulatory roles

Cited by 1,037 publications

References 0 publications

Plasticity of Dopamine D4 Receptors in Rat Forebrain Temporal Association with Motor Hyperactivity Following Neonatal 6-Hydroxydopamine Lesioning

Plasticity of Dopamine D4 Receptors in Rat Forebrain Temporal Association with Motor Hyperactivity Following Neonatal 6-Hydroxydopamine Lesioning

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice

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