Long-Term Abstinence from Developmental Cocaine Exposure Alters Arc/Arg3.1 Modulation in the Rat Medial Prefrontal Cortex

Caffino, Lucia; Giannotti, Giuseppe; Malpighi, Chiara; Racagni, Giorgio; Filip, Małgorzata; Fumagalli, Fabio

doi:10.1007/s12640-014-9472-1

Cited by 11 publications

(12 citation statements)

References 27 publications

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“…Developmental exposure to cocaine increased both FGF-2 and BDNF expression in the mPFC following long-term, but not short-term, withdrawal (Fig 3) (Giannotti et al, 2013;Giannotti et al, 2014;Giannotti et al, 2016). This confirms the enduring effects of early exposure to the psychostimulant and corroborates the impact of withdrawal on brain homeostasis.…”

Section: Effects Of Adolescent Cocaine On Neuroplasticity: the Role Of Trophic Factorsmentioning

confidence: 59%

The effects of cocaine exposure in adolescence: Behavioural effects and neuroplastic mechanisms in experimental models

Caffino

Mottarlini

Zita

et al. 2021

British J Pharmacology

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Drug addiction is a devastating disorder with a huge economic and social burden for modern society. While an individual may slip into drug abuse throughout his/her life, adolescents are at higher risk but, up to date, only few studies attempted to elucidate the underlying cellular and molecular bases of such vulnerability. Indeed, preclinical evidence indicates that psychostimulants and adolescence interact and contribute to promoting a dysfunctional brain.In this review, we have focused our attention primarily on changes in neuroplasticity brought about by cocaine, taking into account that evidence from exposure to cocaine in adolescence is limited in magnitude when comparing to adulthood. This review clearly shows that exposure to cocaine during adolescence, be it acute or chronic, as well as contingent or noncontingent, confers a vulnerable endophenotype by primarily causing changes in neuroplasticity. Given the tight relationship between drug abuse and psychiatric disorders, we will also discuss the translational implications providing an interpretative framework for clinical studies involving addictive as well as affective or psychotic behaviors.

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Section: Effects Of Adolescent Cocaine On Neuroplasticity: the Role Of Trophic Factorsmentioning

confidence: 59%

The effects of cocaine exposure in adolescence: Behavioural effects and neuroplastic mechanisms in experimental models

Caffino

Mottarlini

Zita

et al. 2021

British J Pharmacology

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“…Arc could be considered a key regulator of protein synthesis-dependent forms of synaptic plasticity, which are thought to underlie memory storage [49]. In rats, single or repeated cocaine treatment, as well as long-term abstinence (48 days) following drug administration, all increase Arc expression [50][51][52], although it is associated, at the same time, with alterations in the finely tuned mechanisms that regulate Arc degradation [52]. In our experiments, MDMA increased Arc transcript and protein expression after two weeks of withdrawal, which was also evident, although reduced, after 3 months of withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Adaptive Plasticity in the Hippocampus of Young Mice Intermittently Exposed to MDMA Could Be the Origin of Memory Deficits

et al. 2015

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Concise title: Adaptive plasticity in the hippocampus of young mice exposed to MDMA 2 ABSTRACT (±)3,4-methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic neurotoxin in mice. This study was designed to evaluate whether MDMA exposure affects their recognition memory and hippocampal expression of plasticity markers. Mice were administered with increasing doses of MDMA once per week for 8 weeks (three times in one day, every 3h) and sacrificed two weeks (2 w) or three months (3 m) later. The treatment did not modify hippocampal tryptophan hydroxylase 2, a serotonergic indicator, but induced an initial reduction in dopaminergic markers in substantia nigra, which remained stable for at least 3 months. In parallel, MDMA produced a decrease in dopamine (DA) levels in the striatum at 2 w, which were restored 3 months later, suggesting dopaminergic terminal regeneration (sprouting phenomenon). Moreover, recognition memory was assessed using the object recognition test. Young (2 w) and mature (3 m) adult mice exhibited impaired memory after 24 h but not after just 1 h retention interval. Two weeks after the treatment, animals showed constant levels of CREB but an increase in its phosphorylated form and in cFos expression. BDNF and especially Arc overexpression was sustained and long lasting.We cannot rule out the absence of MDMA injury in the hippocampus being due to the generation of BDNF. The levels of NMDAR2B, PSD-95 and synaptophysin were unaffected.In conclusion, the young mice exposed to MDMA showed increased expression of early key markers of plasticity, which sometimes remained for three months, and suggests hippocampal maladaptive plasticity that could explain memory deficits evidenced here.

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“…Most notably, expression of several E3 ubiquitin ligases, which catalyze ubiquitin transfer to a specific substrate before its degradation in proteasomes [40], was selectively elevated in CeA on withdrawal day 35 in the Meth but not Saline group. This finding is novel because very few studies to our knowledge have determined the role of E3 ubiquitin ligases in the behavioral effects of addictive drugs [41,42]. Jiao et al [41] reported that expression of Synovial apoptosis inhibitor 1, an E3 ubiquitin ligase, in dorsal striatum increases after Meth CPP, which leads to degradation of the GABAA1 receptor subunit.…”

Section: Distinct Transcriptional Regulation Of Cea and Ofc During Inmentioning

confidence: 86%

“…Jiao et al [41] reported that expression of Synovial apoptosis inhibitor 1, an E3 ubiquitin ligase, in dorsal striatum increases after Meth CPP, which leads to degradation of the GABAA1 receptor subunit. Caffino, et al [42] reported that exposure to cocaine during adolescence is associated with increased ubiquitin-protein ligase E3A in medial prefrontal cortex, which leads to Arc protein degradation in adulthood. Among the E3 ubiquitin ligases observed in our study, two of them are of interest.…”

Section: Distinct Transcriptional Regulation Of Cea and Ofc During Inmentioning

confidence: 99%

Genome-wide transcriptional profiling of central amygdala and orbitofrontal cortex during incubation of methamphetamine craving

Cates

Purushothaman

et al. 2018

Neuropsychopharmacol

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Methamphetamine (Meth) seeking progressively increases after withdrawal (incubation of Meth craving), but the transcriptional mechanisms that contribute to this incubation are unknown. Here we used RNA-sequencing to analyze transcriptional profiles associated with incubation of Meth craving in central amygdala (CeA) and orbitofrontal cortex (OFC), two brain areas previously implicated in relapse to drug seeking. We trained rats to self-administer either saline (control condition) or Meth (10 days; 9 h/day, 0.1 mg/kg/infusion). Next, we collected brain tissue from CeA and OFC on withdrawal day 2 (when Meth seeking is low and non-incubated) and on day 35 (when Meth seeking is high and incubated), for subsequent RNA-sequencing. In CeA, we identified 10-fold more differentially expressed genes (DEGs) on withdrawal day 35 than day 2. These genes were enriched for several biological processes, including protein ubiquitination and histone methylation. In OFC, we identified much fewer expression changes than in CeA, with more DEGs on withdrawal day 2 than on day 35. There was a significant overlap between upregulated genes on withdrawal day 2 and downregulated genes on withdrawal day 35 in OFC. Our analyses highlight the CeA as a key region of transcriptional regulation associated with incubation of Meth seeking. In contrast, transcriptional regulation in OFC may contribute to Meth seeking during early withdrawal. Overall, these findings provide a unique resource of gene expression data for future studies examining transcriptional mechanisms in CeA that mediate Meth seeking after prolonged withdrawal.

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Long-Term Abstinence from Developmental Cocaine Exposure Alters Arc/Arg3.1 Modulation in the Rat Medial Prefrontal Cortex

Cited by 11 publications

References 27 publications

The effects of cocaine exposure in adolescence: Behavioural effects and neuroplastic mechanisms in experimental models

The effects of cocaine exposure in adolescence: Behavioural effects and neuroplastic mechanisms in experimental models

Adaptive Plasticity in the Hippocampus of Young Mice Intermittently Exposed to MDMA Could Be the Origin of Memory Deficits

Genome-wide transcriptional profiling of central amygdala and orbitofrontal cortex during incubation of methamphetamine craving

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