Delayed plasticity of the mesolimbic dopamine system following neonatal 6-OHDA lesions

Frohna, Paul; Neal-Beliveau, Bethany S.; Joyce, Jeffrey N.

doi:10.1002/(sici)1098-2396(199703)25:3<293::aid-syn9>3.0.co;2-6

Cited by 20 publications

(6 citation statements)

References 44 publications

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“…The reduced levels of Cdkn1c expression among low-LG offspring at P6 may thus delay development of the VTA and contribute to the reduced number of DA cells. Similar effects are observed following neonatal 6-hydroxydopamine lesions (Frohna et al, 1997). Although we did not observe any effects of maternal care on Nurr1, increased TH immunoreactivity resulting from prolonged membrane polarisation has been demonstrated in cell culture in the absence of altered Nurr1 immunoreactivity or Nurr1 mRNA levels (He et al, 2011).…”

Section: Discussionsupporting

confidence: 82%

Effects of maternal care on the development of midbrain dopamine pathways and reward‐directed behavior in female offspring

Peña

Neugut

Calarco

et al. 2014

Eur J of Neuroscience

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Variation within mesolimbic dopamine (DA) pathways has significant implications for behavioral responses to rewards, and previous studies have indicated long-term programming effects of early life stress on these pathways. In the current study, we examined the impact of natural variations in maternal care in Long Evans rats on the development of DA pathways in female offspring and the consequences for reward-directed behaviors. We found that tyrosine hydroxylase (TH) immunoreactivity in the ventral tegmental area was elevated by postnatal day 6 in response to maternal licking/grooming (LG), and that these effects were sustained into adulthood. Increased TH immunoreactivity was not found to be associated with altered epigenetic regulation or transcriptional activation of Th, but probably involved LG-associated changes in the differentiation of postnatal DA neurons through increased expression of Cdkn1c, and enhanced survival of DA projections through LG-associated increases in Lmx1b and brain-derived neurotrophic factor. At weaning, high-LG offspring had elevated DA receptor mRNA levels within the nucleus accumbens and increased conditioned place preference for a high-fat diet. In contrast, high-LG, as compared with low-LG, juvenile offspring had a reduced preference for social interactions with siblings, and haloperidol administration abolished group differences in conditioned place preference through a shift towards increased social preferences in high-LG offspring. The effects of maternal care on developing DA pathways and reward-directed behavior of female offspring that we have observed may play a critical role in the behavioral transmission of maternal LG from mother to daughter, and account for individual differences in the mesolimbic DA system.

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Section: Discussionsupporting

confidence: 82%

Effects of maternal care on the development of midbrain dopamine pathways and reward‐directed behavior in female offspring

Peña

Neugut

Calarco

et al. 2014

Eur J of Neuroscience

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“…Whereas gradual recovery of tyrosine hydroxylase (TH) immunoreactivity has been reported (Frohna et al 1997), slowly progressive loss of DA content was noted after more complete lesions (Teicher et al 1998). Recovery of DAT levels in NAc at PD 37 and 60 in the present study (Figure 3) may indicate repair or regrowth of DA projections from ventral tegmental area to NAc.…”

Section: Discussionsupporting

confidence: 47%

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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“…With development, this imbalance decreases due to an inter-hemispheric time-dependent regulatory mechanism which differentially influences the DA system in each hemisphere (Rodriguez et al, 1994; Giardino, 1996; Frohna et al, 1997; Vernaleken et al, 2007). This mechanism also compensates for alterations in the endogenous DA imbalance following brain lesion and possibly neurodegenerative processes.…”

Section: Discussionmentioning

confidence: 99%

“…A clue for reconciling this discrepancy may be found in reports describing an inter-hemispheric regulatory/compensatory process which acts differentially in both hemispheres to restore DAergic balance. Such a process has been suggested to be active during development (Rodriguez et al, 1994; Giardino, 1996; Frohna et al, 1997; Vernaleken et al, 2007) and following tissue damage (Altar et al, 1983; Pritzel et al, 1983; Carlson et al, 1996; Roedter et al, 2001; Blesa et al, 2011). This regulatory/compensatory process which is time-dependent utilizes mechanisms of action such as controlling the ratio of D1/D2 receptors (Joyce, 1991a,b), changing the number of synaptic terminals (Jaeger et al, 1983; Lawler et al, 1995; Meshul et al, 1999; Gittis et al, 2011; Golden et al, 2013), and enhancing DA turnover and release from the available fibers (Ikegami et al, 2006).…”

Section: Endogenous Asymmetry In the Daergic Systemmentioning

confidence: 99%

Hemispheric differences in the mesostriatal dopaminergic system

Molochnikov

Cohen

2014

Front. Syst. Neurosci.

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The mesostriatal dopaminergic system, which comprises the mesolimbic and the nigrostriatal pathways, plays a major role in neural processing underlying motor and limbic functions. Multiple reports suggest that these processes are influenced by hemispheric differences in striatal dopamine (DA) levels, DA turnover and its receptor activity. Here, we review studies which measured the concentration of DA and its metabolites to examine the relationship between DA imbalance and animal behavior under different conditions. Specifically, we assess evidence in support of endogenous, inter-hemispheric DA imbalance; determine whether the known anatomy provides a suitable substrate for this imbalance; examine the relationship between DA imbalance and animal behavior; and characterize the symmetry of the observed inter-hemispheric laterality in the nigrostriatal and the mesolimbic DA systems. We conclude that many studies provide supporting evidence for the occurrence of experience-dependent endogenous DA imbalance which is controlled by a dedicated regulatory/compensatory mechanism. Additionally, it seems that the link between DA imbalance and animal behavior is better characterized in the nigrostriatal than in the mesolimbic system. Nonetheless, a variety of brain and behavioral manipulations demonstrate that the nigrostriatal system displays symmetrical laterality whereas the mesolimbic system displays asymmetrical laterality which supports hemispheric specialization in rodents. The reciprocity of the relationship between DA imbalance and animal behavior (i.e., the capacity of animal training to alter DA imbalance for prolonged time periods) remains controversial, however, if confirmed, it may provide a valuable non-invasive therapeutic means for treating abnormal DA imbalance.

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Delayed plasticity of the mesolimbic dopamine system following neonatal 6-OHDA lesions

Cited by 20 publications

References 44 publications

Effects of maternal care on the development of midbrain dopamine pathways and reward‐directed behavior in female offspring

Effects of maternal care on the development of midbrain dopamine pathways and reward‐directed behavior in female offspring

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

Hemispheric differences in the mesostriatal dopaminergic system

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