ReviewFrom Signaling Molecules to Circuits and Behaviors: Cell-Type–Specific Adaptations to Psychostimulant Exposure in the Striatum
Section snippets
Cell-Type–Specific Modulation of SPN Activity
A current hypothesis is that the transition from recreational to compulsive drug use relies on a gradual recruitment from ventromedial to dorsolateral striatal subregions (18,19). Despite the existence of behavioral features of vulnerability toward addiction (19), few preclinical studies support the intriguing possibility that individuals who develop behavioral traits of addiction display plasticity-related alterations in the striatum (20). Nonetheless, most studies have focused on remodeling
Cell-Type–Specific Striatal Signaling From the Membrane Toward the Nucleus
Through differential coupling of DA receptors to Gs/olf and Gi/o, DA activates the cAMP (cyclic adenosine monophosphate)/downstream PKA (protein kinase A) pathway in D1R-SPNs, while repressing it in D2R-SPNs, leading to opposite regulations of ion channels, including glutamate receptors (69, 70, 71). The consensus is that DA increase facilitates glutamate-dependent activation of D1R-SPNs and inhibits glutamate-dependent activation of D2R-SPNs. Accordingly, acute cocaine administration triggers
Genetic and Epigenetic Regulation
Like other forms of memory, addiction-related memories require changes in gene regulation and protein expression (107,108) taking place downstream from the activation of cytoplasm-to-nucleus signaling. Once activated in D1R-SPNs (24), ERK directly targets the transcription factor Elk-1 (ETS-like-1 protein) and indirectly the Ca2+-binding protein and CREB (cAMP-responsive element binding protein) via the MSK-1 (mitogen and stress-activated protein kinase-1) (109, 110, 111). Cocaine-triggered
Conclusions and Perspectives
While converging data point at a critical role for D1R-SPN-specific plasticity, cell-type–specific approaches reveal evident molecular alterations in D2R-SPNs in favor of their active role in the reshaping of striatal circuits in addiction. However, we still lack a comprehensive model for the contribution of intracellular pathways involved in drug-induced transcriptional alterations in D1R-SPNs and D2R-SPNs at various stages of addiction. Cell-type–specific approaches and timed-controlled
Acknowledgments and Disclosures
The work is supported by the Centre National de la Recherche Scientifique (to MS, PV, and JC), Institut National de la Santé et de la Recherche Médicale (to PV and JC), Fondation pour la Recherche Médicale (Grant No. DEQ20150734352 [to JC]), and the Bio-Psy Labex cluster of excellence (to MS, JC, and PV); Sorbonne Université—Paris VI (to JC and PV), Agence Nationale pour la Recherche (Grant Nos. ANR-15-CE16-001 [to PT and PV] and ANR-18-CE37-0003-02 [to PV]); and the Institut National de la
References (149)
- et al.
Drug-evoked synaptic plasticity in addiction: From molecular changes to circuit remodeling
Neuron
(2011) - et al.
The persistence of maladaptive memory: Addiction, drug memories and anti-relapse treatments
Neurosci Biobehav Rev
(2012) - et al.
The molecular basis of drug addiction: Linking epigenetic to synaptic and circuit mechanisms
Neuron
(2019) - et al.
Parallel and interactive learning processes within the basal ganglia: Relevance for the understanding of addiction
Behav Brain Res
(2009) - et al.
Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry
Neuron
(2014) - et al.
The Projection Targets of Medium Spiny Neurons Govern Cocaine-Evoked Synaptic Plasticity in the Nucleus Accumbens
Cell Rep
(2019) - et al.
The functional anatomy of basal ganglia disorders
Trends Neurosci
(1989) Primate models of movement disorders of basal ganglia origin
Trends Neurosci
(1990)- et al.
Optogenetics reveals a role for accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization
Front Behav Neurosci
(2014) - et al.
Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior
Neuron
(2010)
Accumbal D1R neurons projecting to lateral hypothalamus authorize feeding
Neuron
Dopamine regulation of lateral inhibition between striatal neurons gates the stimulant actions of cocaine
Neuron
Striatal local circuitry: A new framework for lateral inhibition
Neuron
Cocaine inhibition of synaptic transmission in the ventral pallidum is pathway-specific and mediated by serotonin
Cell Rep
Direct and indirect dorsolateral striatum pathways reinforce different action strategies
Curr Biol
Complementary contributions of striatal projection pathways to action initiation and execution
Cell
Convergence of reinforcing and anhedonic cocaine effects in the ventral pallidum
Neuron
Cocaine-induced structural plasticity in input regions to distinct cell types in nucleus accumbens
Biol Psychiatry
Cocaine place conditioning strengthens location-specific hippocampal coupling to the nucleus accumbens
Neuron
Molecular neuroscience in the 21st century: A personal perspective
Neuron
Spatially compact neural clusters in the dorsal striatum encode locomotion relevant information
Neuron
GluN1 deletions in D1- and A2A-expressing cell types reveal distinct modes of behavioral regulation
Neuropharmacology
Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory
Neuron
Cyclic adenosine monophosphate–independent tyrosine phosphorylation of NR2B mediates cocaine-induced extracellular signal-regulated kinase activation
Biol Psychiatry
ERK2: A logical AND gate critical for drug-induced plasticity?
Curr Opin Pharmacol
Extracellular signal-regulated protein kinases 1 and 2 activation by addictive drugs: A signal toward pathological adaptation
Biol Psychiatry
Rapid synaptogenesis in the nucleus accumbens is induced by a single cocaine administration and stabilized by mitogen-activated protein kinase interacting kinase-1 activity
Biol Psychiatry
In vivo veritas, the next frontier for functionally selective GPCR ligands
Methods
Interactions between NMDA and dopamine receptors: A potential therapeutic target
Brain Res
Diversity and bias through dopamine D2R heteroreceptor complexes
Curr Opin Pharmacol
Molecular basis of long-term plasticity underlying addiction
Nat Rev Neurosci
Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats
Proc Natl Acad Sci U S A
A dopaminergic axon lattice in the striatum and its relationship with cortical and thalamic terminals
J Neurosci
Cortical and thalamic innervation of direct and indirect pathway medium-sized spiny neurons in mouse striatum
J Neurosci
D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons
Science
D1 and D2 dopamine receptor gene expression in the rat striatum: Sensitive cRNA probes demonstrate prominent segregation of D1 and D2 mRNAS in distinct neuronal populations of the dorsal and ventral striatum
J Comp Neurol
A transduction pathway associated with receptors coupled to the inhibitory guanine nucleotide binding protein Gi that amplifies ATP-mediated arachidonic acid release
Proc Natl Acad Sci U S A
Gαolf is necessary for coupling D1 and A2a receptors to adenylyl cyclase in the striatum
J Neurochem
Dopamine receptor subtypes in reward and relapse
A gene expression atlas of the central nervous system based on bacterial artificial chromosomes
Nature
Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs
J Neurosci
Expression of the Cre recombinase in dopaminoceptive neurons
BMC Neurosci
Drd1a-tdTomato BAC transgenic mice for simultaneous visualization of medium spiny neurons in the direct and indirect pathways of the basal ganglia
J Neurosci
D2R striatopallidal neurons inhibit both locomotor and drug reward processes
Nat Neurosci
Drug addiction: Updating actions to habits to compulsions ten years on
Annu Rev Psychol
Transition to addiction is associated with a persistent impairment in synaptic plasticity
Science
Striatal cholinergic interneuron regulation and circuit effects
Front Synaptic Neurosci
Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin
J Neurosci
Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol
J Neurosci
Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections
Nat Neurosci
Cited by (24)
Targeting the cytoskeleton as a therapeutic approach to substance use disorders
2024, Pharmacological ResearchCotransplantation of NSCs and ethyl stearate promotes synaptic plasticity in PD rats by Drd1/ERK/AP-1 signaling pathway
2024, Journal of EthnopharmacologyPrenatal exposition to haloperidol: A preclinical narrative review
2023, Neuroscience and Biobehavioral ReviewsThe differential vulnerabilities of Per2 knockout mice to the addictive properties of methamphetamine and cocaine
2023, Progress in Neuro-Psychopharmacology and Biological Psychiatry