Netrin-1 receptor-deficient mice show age-specific impairment in drug-induced locomotor hyperactivity but still self-administer methamphetamine

Kim, Jee Hyun; Lavan, Doron; Chen, Nicola; Flores, Cecilia; Cooper, Helen; Lawrence, Andrew J

doi:10.1007/s00213-013-3187-5

Cited by 19 publications

(15 citation statements)

References 45 publications

(56 reference statements)

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“…The latter effects result from ectopic growth of mesolimbic dopamine axons to the PFC, a concomitant increase in mesocortical dopamine synapses [8], function [47], and augmented cortical inhibitory control over the responsiveness of mesolimbic dopamine neurons [48]. These changes are concordant with the findings that, as adults, but not as adolescents, Dcc +/− mice display multiple alterations to dopamine-related behaviors, including diminished sensitivity to the effects of stimulant drugs (cocaine, amphetamine, methamphetamine) on locomotor activity, sensorimotor gating, conditioned place preference, and intracranial selfstimulation [6,42,49,50]. These behavioral effects have been observed primarily under pharmacological challenge conditions but drug-free adult DCC-deficient mice exhibit reduced impulsivity [8] and attend less to a novel object in the presence of a familiar object [51].…”

Section: Netrin-1 and Its DCC Receptorsupporting

confidence: 78%

The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

2019

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Axon guidance molecules direct growing axons toward their targets, assembling the intricate wiring of the nervous system. One of these molecules, Netrin-1, and its receptor, DCC (deleted in colorectal cancer), has profound effects, in laboratory animals, on the adolescent expansion of mesocorticolimbic pathways, particularly dopamine. Now, a rapidly growing literature suggests that (1) these same alterations could occur in humans, and (2) genetic variants in Netrin-1 and DCC are associated with depression, schizophrenia, and substance use. Together, these findings provide compelling evidence that Netrin-1 and DCC influence mesocorticolimbic-related psychopathological states that emerge during adolescence.

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Section: Netrin-1 and Its DCC Receptorsupporting

confidence: 78%

The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

2019

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“…For example, it is unclear whether receptor pruning reflects increased turnover or reduced synthesis and expression of D1 and D2 proteins, or whether it reflects programmed cell death or apoptosis of D1 and D2 expressing neurons (Marti, James, Oo, Kelly, & Burke, 1997). In addition, dopaminergic innervation continues from birth into adulthood, however how this effects the expression of D1 and D2 receptors is poorly understood (Kim et al, 2013;Reynolds et al, 2018).…”

Section: Limitationsmentioning

confidence: 99%

Postnatal developmental trajectory of dopamine receptor 1 and 2 expression in cortical and striatal brain regions

Cullity

Madsen

Perry

et al. 2018

J of Comparative Neurology

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Healthy brain function requires a balance between the activity of dopamine receptor 1 (D1) and dopamine receptor 2 (D2). Alterations in this balance increase the risk for numerous developmental brain disorders. Indeed, D1 and D2 expression fluctuates throughout maturation, although there is conflicting evidence regarding the precise changes that occur. Here, we used stereology to investigate the developmental changes in the number of D1‐ or D2‐expressing neurons in the prelimbic cortex, infralimbic cortex (IL), insula cortex, dorsal striatum, and ventral striatum of female and male mice with green fluorescent protein‐tagged D1 or D2. Postnatal day 17, 25, 35, 49, and 70 were examined to cover juvenility to adulthood. In all regions, analysis of D1 density compared to D2 density within each sex seldom detected effects or interactions involving age. However, D1:D2 density ratio changed across age depending on sex. In the IL, D1:D2 density ratio increased in females from adolescence, whereas it was stable in males. In the insula cortex, D1:D2 ratio initially increased in males but decreased in females from juvenility to preadolescence. The ratio then increased in males and females from adolescence to adulthood, with males showing a more dramatic increase. In both the dorsal and ventral striatum, the ratio increased from adolescence. In all regions, females had a higher ratio compared to males throughout maturation except in the insula cortex at P25. These comprehensive observations are novel, and highlight how the maturational changes in the expression of these receptors may contribute to developmental disorders.

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“…DCC haploinsufficient mice display blunted motor responses to amphetamine (Flores et al 2005;Kim et al 2013). These findings suggest that netrin-1 and DCC may influence the neural control of motor behaviour in rodents.…”

Section: Conditional Deletion Of Netrin-1 Does Not Influence Novelty-mentioning

confidence: 99%

Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain.

Wong

Glasgow

Trigiani

et al. 2018

Preprint

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Netrin-1 was initially characterized as an axon guidance molecule that is essential for normal embryonic neural development; however, many types of neurons continue to express netrin-1 in the post-natal and adult mammalian brain. Netrin-1 and the netrin receptor DCC are both enriched at synapses. In the adult hippocampus, activity-dependent secretion of netrin-1 by neurons potentiates glutamatergic synapse function, and is critical for long-term potentiation, an experimental cellular model of learning and memory. Here, we assessed the impact of neuronal expression of netrin-1 in the adult brain on behavior using tests of learning and memory. We show that adult mice exhibit impaired spatial memory following conditional deletion of netrin-1 from glutamatergic neurons in the hippocampus and neocortex. Further, we provide evidence that mice with conditional deletion of netrin-1 do not display aberrant anxiety-like phenotypes and show a reduction in self-grooming behaviour. These findings reveal a critical role for netrin-1 expressed by neurons in the regulation of spatial memory formation.

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Netrin-1 receptor-deficient mice show age-specific impairment in drug-induced locomotor hyperactivity but still self-administer methamphetamine

Cited by 19 publications

References 45 publications

The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

Postnatal developmental trajectory of dopamine receptor 1 and 2 expression in cortical and striatal brain regions

Spatial memory formation requires netrin-1 expression by neurons in the adult mammalian brain.

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