Resilience to amphetamine in mouse models of netrin-1 haploinsufficiency: role of mesocortical dopamine

Pokinko, Matthew; Moquin, Luc; Torres‐Berrío, Angélica; Gratton, Alain; Flores, Cecilia

doi:10.1007/s00213-015-4032-9

Cited by 19 publications

(22 citation statements)

References 73 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have found that, as adults, mice with Dcc haploinsufficiency are protected against all these effects [49,59,66–68]. Furthermore, we recently demonstrated that increased input and concentration of dopamine in the medial prefrontal cortex directly causes the effects on locomotor activity [69], and we expect that the same is true for the other effects.…”

Section: By Organizing Dopamine Development DCC Receptors Determine mentioning

confidence: 92%

Making Dopamine Connections in Adolescence

Hoops

Flores

2017

Trends in Neurosciences

Self Cite

122

View full text Add to dashboard Cite

A dramatic maturational process ongoing in adolescence is prefrontal cortex development, including its dopamine innervation. Dopamine axons grow from the striatum to the prefrontal cortex, the only known case of long-distance axon growth during adolescence. This is coordinated by the Netrin-1 guidance cue receptor DCC, which in turn controls the intrinsic development of the prefrontal cortex itself. Stimulant drugs in adolescence alter DCC in dopamine neurons and in turn prefrontal cortex maturation, impacting cognitive abilities. Variations in DCC expression are linked to psychiatric conditions of prefrontal cortex dysfunction, and microRNA regulation of DCC may be key to determining adolescent vulnerability or resilience. Since early interventions are proving to effectively ameliorate disease outcome, the Netrin-1 system is a promising therapeutic target.

show abstract

Section: By Organizing Dopamine Development DCC Receptors Determine mentioning

confidence: 92%

Making Dopamine Connections in Adolescence

Hoops

Flores

2017

Trends in Neurosciences

Self Cite

122

View full text Add to dashboard Cite

show abstract

“…In comparison, in the NAcc, there are decreases in dopamine varicosities and amphetamine-induced dopamine release [8,42,45,46]. 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].…”

Section: Netrin-1 and Its DCC Receptormentioning

confidence: 99%

“…Behavioral and neurochemical effects of DCC haploinsufficiency are mirrored by Netrin-1 haploinsufficiency. In adulthood, but not in adolescence, Netrin-1 haploinsufficient mice exhibit increased medial PFC (mPFC) dopamine concentrations and reduced sensitivity to the behavioral effects of amphetamine [48]. Finally, adolescent amphetamine administration alters the expression of both DCC in dopamine neurons and Netrin-1 in the NAcc and mPFC [52].…”

Section: Netrin-1 and Its DCC Receptormentioning

confidence: 99%

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

2019

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…During adolescence, DCC receptor signaling within dopamine neurons controls the extent of dopamine innervation to the mPFC (Manitt et al, 2013). DCC receptors in turn: (a) dictate the structure and excitability of adult mPFC pyramidal neurons (Grant et al, 2007, Manitt et al, 2011), (b) fine-tune cognitive flexibility and behavioral inhibition (Manitt et al, 2013, Reynolds et al, 2015b) and (c) determine the control that mPFC dopamine exerts over mesolimbic dopamine neurons (Pokinko et al, 2015). Dcc haploinsufficiency leads to increased mPFC dopamine input, which causes improved cognitive processing and resilience to the behavioral effects of stimulant drugs of abuse in adulthood (Grant et al, 2007, Reynolds et al, 2015a).…”

mentioning

confidence: 99%

Dcc haploinsufficiency regulates dopamine receptor expression across postnatal lifespan

et al. 2017

Self Cite

View full text Add to dashboard Cite

Adolescence is a period during which the medial prefrontal cortex (mPFC) undergoes significant remodeling. The netrin-1 receptor, DCC, controls the extent and organization of mPFC dopamine connectivity during adolescence and in turn directs mPFC functional and structural maturation. Dcc haploinsufficiency leads to increased mPFC dopamine input, which causes improved cognitive processing and resilience to behavioral effects of stimulant drugs of abuse. Here we examine the effects of Dcc haploinsufficiency on the dynamic expression of dopamine receptors in forebrain targets of C57BL6 mice. We conducted quantitative receptor autoradiography experiments with [3H]SCH-23390 or [3H]raclopride to characterize D1 and D2 receptor expression in mPFC and striatal regions in male Dcc haploinsufficient and wild-type mice. We generated autoradiograms at early adolescence (PND21±1), mid-adolescence (PND35±2), and adulthood (PND75±15). C57BL6 mice exhibit overexpression and pruning of D1, but not D2, receptors in striatal regions, and a lack of dopamine receptor pruning in the mPFC. We observed age- and region-specific differences in D1 and D2 receptor density between Dcc haploinsufficient and wild-type mice. Notably, neither group shows the typical pattern of mPFC dopamine receptor pruning in adolescence, but adult haploinsufficient mice show increased D2 receptor density in the mPFC. These results show that DCC receptors contribute to the dynamic refinement of D1 and D2 receptor expression in striatal regions across adolescence. The age-dependent expression of dopamine receptor in C57BL6 mice shows marked differences from previous characterizations in rats.

show abstract

Resilience to amphetamine in mouse models of netrin-1 haploinsufficiency: role of mesocortical dopamine

Cited by 19 publications

References 73 publications

Making Dopamine Connections in Adolescence

Making Dopamine Connections in Adolescence

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

Dcc haploinsufficiency regulates dopamine receptor expression across postnatal lifespan

Contact Info

Product

Resources

About