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Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.
Brain Res Bull. 2017 Sep; 134:246-252.BR

Abstract

CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [[3]H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal levels of DOPET. At the same concentration, 0.1μM, CART (55-102) peptide did not have any effect on the release of noradrenaline. In the presence of CART (55-102) peptide, 0.1μM, the effect of cocaine, 30μM, on the basal dopamine release was inhibited and the effect on the basal DOPAC release substantially increased. To our knowledge, our findings are the first to show direct neurochemical evidence that CART (55-102) peptide plays a neuromodulatory role on the dopaminergic reward system by decreasing dopamine in the mouse nucleus accumbens and by attenuating cocaine-induced effects on dopamine release.

Authors+Show Affiliations

Lab. "Neuropeptides", Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113, Sofia, Bulgaria. Electronic address: arakovska@yahoo.com.Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083, Budapest, Hungary.Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, H-1083, Budapest, Hungary.Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. bl. 21, 1113, Sofia, Bulgaria.Faculty of Biology, Sofia University St. Kliment Ohridski, Dragan Tsankov Str. 8, 1164, Sofia, Bulgaria.Lab. "Neuropeptides", Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., bl. 23, 1113, Sofia, Bulgaria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28802898

Citation

Rakovska, Angelina, et al. "Neurochemical Evidence That Cocaine- and Amphetamine-regulated Transcript (CART) 55-102 Peptide Modulates the Dopaminergic Reward System By Decreasing the Dopamine Release in the Mouse Nucleus Accumbens." Brain Research Bulletin, vol. 134, 2017, pp. 246-252.
Rakovska A, Baranyi M, Windisch K, et al. Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens. Brain Res Bull. 2017;134:246-252.
Rakovska, A., Baranyi, M., Windisch, K., Petkova-Kirova, P., Gagov, H., & Kalfin, R. (2017). Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens. Brain Research Bulletin, 134, 246-252. https://doi.org/10.1016/j.brainresbull.2017.08.005
Rakovska A, et al. Neurochemical Evidence That Cocaine- and Amphetamine-regulated Transcript (CART) 55-102 Peptide Modulates the Dopaminergic Reward System By Decreasing the Dopamine Release in the Mouse Nucleus Accumbens. Brain Res Bull. 2017;134:246-252. PubMed PMID: 28802898.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens. AU - Rakovska,Angelina, AU - Baranyi,Maria, AU - Windisch,Katalin, AU - Petkova-Kirova,Polina, AU - Gagov,Hristo, AU - Kalfin,Reni, Y1 - 2017/08/09/ PY - 2017/05/22/received PY - 2017/07/05/revised PY - 2017/08/07/accepted PY - 2017/8/15/pubmed PY - 2018/5/8/medline PY - 2017/8/14/entrez KW - CART (55–102) peptide KW - Cocaine KW - Dopamine release KW - Nucleus accumbens SP - 246 EP - 252 JF - Brain research bulletin JO - Brain Res Bull VL - 134 N2 - CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [[3]H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal levels of DOPET. At the same concentration, 0.1μM, CART (55-102) peptide did not have any effect on the release of noradrenaline. In the presence of CART (55-102) peptide, 0.1μM, the effect of cocaine, 30μM, on the basal dopamine release was inhibited and the effect on the basal DOPAC release substantially increased. To our knowledge, our findings are the first to show direct neurochemical evidence that CART (55-102) peptide plays a neuromodulatory role on the dopaminergic reward system by decreasing dopamine in the mouse nucleus accumbens and by attenuating cocaine-induced effects on dopamine release. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/28802898/Neurochemical_evidence_that_cocaine__and_amphetamine_regulated_transcript__CART__55_102_peptide_modulates_the_dopaminergic_reward_system_by_decreasing_the_dopamine_release_in_the_mouse_nucleus_accumbens_ DB - PRIME DP - Unbound Medicine ER -