CART peptide and opioid addiction: Expression changes in male rat brain

Bakhtazad, Atefeh; Vousooghi, Nasim; Garmabi, Behzad; Zarrindast, M.R.

doi:10.1016/j.neuroscience.2016.02.071

Cited by 19 publications

(11 citation statements)

References 65 publications

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“…Recently, our laboratory reported that the levels of CART mRNA and the peptide is considerably up-regulated in the NAc when rats become addicted to the escalating doses of morphine. Our study showed that CART peptide in the NAc has a crucial role in morphine addiction [13] and morphine-induced sensitization [17]. Elevation of the endogenous CART in the NAc shell following training rats in the Morris water maze demonstrates that CART is involved in the formation of spatial learning and memory [18].…”

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confidence: 62%

“…The peptide takes part in several physiological functions such as learning, memory [11], drug reward, reinforcement, addiction [12], etc. Based on a growing body of evidence, it is believed that CART is involved in the action of psychostimulant and opioid drugs [13][14][15]. CART peptide in the NAc shell acts downstream to dopamine and may work as a mediator in morphine-induced reward and reinforcement [16].…”

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confidence: 99%

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The effect of microinjection of CART 55-102 into the nucleus accumbens shell on morphine-induced conditioned place preference in rats: Involvement of the NMDA receptor

et al. 2020

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BackgroundThe addictive properties of opioids may be mediated to some extent by cocaine-and amphetamineregulated transcript (CART) in the reward pathway. There are also some claims regarding the interaction of CART and glutamate system. Drug-paired learning and memory may induce conditioned place preference (CPP) or conditioned place aversion (CPA). Here, we have evaluated whether intranucleus accumbens (NAc) shell infusions of CART induces CPP or CPA and affect morphine reward. In addition, we have measured the expression of the NR1 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor in various parts of the reward pathway (NAc, prefrontal cortex (PFC), and hippocampus) after conditioning tests. Bilateral cannulas were implanted in the rats NAc shell and then the animals were exposed to place conditioning. Animals were place-conditioned with several doses of subcutaneous (s.c.) morphine prior to the intra-NAc shell infusion of artificial cerebral spinal fluid (aCSF). Immunohistochemistry (IHC) data showed a dose-dependent increase in the expression of the NR1 subunit in all examined parts. Then, rats were conditioned with intra-NAc shell infusion of different doses of CART. CPP and CPA were induced with 2.5 and 5 μg/side, respectively. ResultsIHC showed an elevated level of NR1 with 2.5 μg/side and a decrease with 5 μg/side in all areas.Administration of a sub-rewarding dose of CART (1.25 μg/side) prior to the injection of a subrewarding dose of morphine (2.5 mg/kg) induced CPP and IHC analysis showed an increased amount of NR1 in all examined tissues. However, infusion of an aversive dose of CART (5 μg/side) prior to the injection of a rewarding dose of morphine (5 mg/kg) produced neither CPP nor CPA and IHC data showed a significant decrease in the amount of NR1 subunit in the NAc and hippocampus. ConclusionsIt seems that the rewarding or aversive effects of intra-NAc shell CART and its facilitating or inhibiting effects on morphine reward are dose-dependent. Furthermore, the NMDA receptor may be closely involved in the affective properties of opioids and CART in the reward pathway.

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confidence: 62%

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confidence: 99%

The effect of microinjection of CART 55-102 into the nucleus accumbens shell on morphine-induced conditioned place preference in rats: Involvement of the NMDA receptor

et al. 2020

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“…However, in our study, the gene expression level and methylation level of Oprm1, which encodes µ-opioid receptors, were decreased and increased by DBS, respectively (Supplementary Tables S1 and S4). This indicates that in addition to MOPs, CART may also be involved in morphine addiction-related signaling [54,55]. The CART peptide is known to play a role in regulating the behavioral sensitization induced by psychostimulants [56], and the resulting addiction-related anxious and aversive emotions can lead to depression-like behaviors that may ultimately facilitate suicidal actions possibly mediated by GABAergic pathways [57,58].…”

Section: Discussionmentioning

confidence: 99%

Epitranscriptome of the ventral tegmental area in a deep brain-stimulated chronic unpredictable mild stress mouse model

Song

Gao

et al. 2020

Translational Neuroscience

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Deep brain stimulation (DBS) applied to the nucleus accumbens (NAc) alleviates the depressive symptoms of major depressive disorders. We investigated the mechanism of this effect by assessing gene expression and RNA methylation changes in the ventral tegmental area (VTA) following NAc-DBS in a chronic unpredictable mild stress (CUMS) mouse model of depression. Gene expression and N6-methyladenosine (m6A) levels in the VTA were measured in mice subjected to CUMS and then DBS, and transcriptome-wide m6A changes were profiled using immunoprecipitated methylated RNAs with microarrays, prior to gene ontology analysis. The expression levels of genes linked to neurotransmitter receptors, transporters, transcription factors, neuronal activities, synaptic functions, and mitogen-activated protein kinase and dopamine signaling were upregulated in the VTA upon NAc-DBS. Furthermore, m6A modifications included both hypermethylation and hypomethylation, and changes were positively correlated with the upregulation of some genes. Moreover, the effects of CUMS on gene expression and m6A-mRNA modification were reversed by DBS for some genes. Interestingly, while the expression of certain genes was not changed by DBS, long-term stimulation did alter their m6A modifications. NAc-DBS-induced modifications are correlated largely with upregulation but sometimes downregulation of genes in CUMS mice. Our findings improve the current understanding of the molecular mechanisms underlying DBS effects on depression.

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“…Salas et al [ 23 ] showed that CART mRNA in the NAc was downregulated by acute morphine in rats. Bakhtazad et al [ 35 ] examined levels of CART mRNA and peptide in male rats after administering morphine under several conditions: acute low dose, acute high dose, and chronic escalating doses. Also withdrawal was induced by injections of naloxone.…”

Section: Opiatesmentioning

confidence: 99%

“…These results are clearly compatible with a view that CARTp is involved in the effects of morphine and that they may mediate some of these effects in reward-related anatomical areas. Further, as is mentioned above in Section 2, the effects of opiates on CARTp weaken when the drugs are used repeatedly [ 35 ].…”

Section: Opiatesmentioning

confidence: 99%

CART Peptides and Drugs of Abuse: A Review of Recent Progress

Kuhar

2016

J Drug Alcohol Res

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Earlier studies suggesting an involvement of cocaine and amphetamine regulated transcript peptide (CARTp) in the actions of drugs of abuse are confirmed in the most recent publications. This seems especially true for the psychostimulants where CARTp in the nucleus accumbens inhibits or regulates the actions of these drugs; the regulation is lost after repeated drug use which may be an important mechanism in addiction. The other drugs, including nicotine, alcohol, opiates, and perhaps caffeine can affect CARTp or CART mRNA levels. While the exact mechanism is not always clear, the hope is that these findings may provide some insight for the development of medications. While binding studies indicate the existence of specific G-protein coupled receptors (GPCR) receptors for CARTp, major work to be done is the cloning of these receptors.

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CART peptide and opioid addiction: Expression changes in male rat brain

Cited by 19 publications

References 65 publications

The effect of microinjection of CART 55-102 into the nucleus accumbens shell on morphine-induced conditioned place preference in rats: Involvement of the NMDA receptor

The effect of microinjection of CART 55-102 into the nucleus accumbens shell on morphine-induced conditioned place preference in rats: Involvement of the NMDA receptor

Epitranscriptome of the ventral tegmental area in a deep brain-stimulated chronic unpredictable mild stress mouse model

CART Peptides and Drugs of Abuse: A Review of Recent Progress

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