CART modulates the effects of levodopa in rat model of Parkinson’s disease

Manoj Upadhya, Gajanan P. Shelkar, Nishikant K. Subhedar, Dadasaheb M. Kokare

Research output: Contribution to journalArticle

Abstract

Parkinson’s disease (PD) is an age-related disorder characterized by a progressive degeneration of dopaminergic neurons of substantia nigra (SN). The neuropeptide cocaine- and amphetamine-regulated transcript (CART) is known to closely interact with the dopamine system and regulate psychomotor activity. We screened the effectiveness of CART in reversing the symptoms of PD in a rat model. PD like condition was induced by administering 6-hydroxydopamine (6-OHDA) directly in the SN of the right side. Fifteen days later, intraperitoneal (IP) treatment with apomorphine hydrochloride to these rats, resulted in contralateral rotations in the rotation test chamber suggesting induction of PD-like symptoms. This action of apomorphine was significantly attenuated by intracerebroventricular (ICV) treatment with CART and potentiated by CART antibody. IP treatment with levodopa also produced contralateral rotation in PD induced rats, and showed anti-Parkinson-like action. Prior treatment with CART via ICV route potentiated the anti-Parkinsonian effects of levodopa, while CART antibody produced opposite effects. CART treatment per se, to PD induced rats produced ipsilateral rotations, suggesting that the peptide may promote the endogenous release of dopamine from intact neurons. While CART-immunoreactivity in arcuate nucleus, paraventricular nucleus, striatum, substantia nigra, ventral tegmental area and locus coeruleus was reduced in the PD induced rats, levodopa treatment restored the expression of CART-immunoreactivity in these nuclei. These results suggest that endogenous CART might closely interact with the dopamine containing SN-striatal pathway which is known to profoundly influence the motor system. The study underscores the importance of CART as a potential therapeutic agent in the treatment of PD.
Original languageEnglish
Pages (from-to)262-272
JournalBehavioural Brain Research
Volume301
DOIs
Publication statusPublished - 15 Mar 2016

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Levodopa
Amphetamine
Cocaine
Parkinson Disease
Substantia Nigra
Apomorphine
Oxidopamine
Dopaminergic Neurons
Dopamine
Corpus Striatum
Arcuate Nucleus of Hypothalamus
Ventral Tegmental Area
Locus Coeruleus
Antibodies
Paraventricular Hypothalamic Nucleus
Neuropeptides
Peptides

Cite this

Upadhya, Manoj ; Shelkar, Gajanan P. ; Subhedar, Nishikant K. ; Kokare, Dadasaheb M. / CART modulates the effects of levodopa in rat model of Parkinson’s disease. In: Behavioural Brain Research. 2016 ; Vol. 301. pp. 262-272.
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abstract = "Parkinson’s disease (PD) is an age-related disorder characterized by a progressive degeneration of dopaminergic neurons of substantia nigra (SN). The neuropeptide cocaine- and amphetamine-regulated transcript (CART) is known to closely interact with the dopamine system and regulate psychomotor activity. We screened the effectiveness of CART in reversing the symptoms of PD in a rat model. PD like condition was induced by administering 6-hydroxydopamine (6-OHDA) directly in the SN of the right side. Fifteen days later, intraperitoneal (IP) treatment with apomorphine hydrochloride to these rats, resulted in contralateral rotations in the rotation test chamber suggesting induction of PD-like symptoms. This action of apomorphine was significantly attenuated by intracerebroventricular (ICV) treatment with CART and potentiated by CART antibody. IP treatment with levodopa also produced contralateral rotation in PD induced rats, and showed anti-Parkinson-like action. Prior treatment with CART via ICV route potentiated the anti-Parkinsonian effects of levodopa, while CART antibody produced opposite effects. CART treatment per se, to PD induced rats produced ipsilateral rotations, suggesting that the peptide may promote the endogenous release of dopamine from intact neurons. While CART-immunoreactivity in arcuate nucleus, paraventricular nucleus, striatum, substantia nigra, ventral tegmental area and locus coeruleus was reduced in the PD induced rats, levodopa treatment restored the expression of CART-immunoreactivity in these nuclei. These results suggest that endogenous CART might closely interact with the dopamine containing SN-striatal pathway which is known to profoundly influence the motor system. The study underscores the importance of CART as a potential therapeutic agent in the treatment of PD.",
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CART modulates the effects of levodopa in rat model of Parkinson’s disease. / Upadhya, Manoj; Shelkar, Gajanan P.; Subhedar, Nishikant K.; Kokare, Dadasaheb M.

In: Behavioural Brain Research, Vol. 301, 15.03.2016, p. 262-272.

Research output: Contribution to journalArticle

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AU - Upadhya, Manoj

AU - Shelkar, Gajanan P.

AU - Subhedar, Nishikant K.

AU - Kokare, Dadasaheb M.

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