title: CART modulates the effects of levodopa in rat model of Parkinson's disease.
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.
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440 033, India.
authors.forename: Manoj A
authors.initials: MA
authors.lastname: Upadhya
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440 033, India.
authors.forename: Gajanan P
authors.initials: GP
authors.lastname: Shelkar
authors.affiliation: Indian Institute of Science Education and Research (IISER), Central Tower, Sai Trinity Building, Garware Circle, Sutarwadi, Pashan, Pune 411 021, Maharashtra, India.
authors.forename: Nishikant K
authors.initials: NK
authors.lastname: Subhedar
authors.affiliation: Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440 033, India. Electronic address: kokaredada@yahoo.com.
authors.forename: Dadasaheb M
authors.initials: DM
authors.lastname: Kokare
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009068:Movement / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D000906:Antibodies; D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D007980:Levodopa; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine
keywords: Cocaine- and amphetamine-regulated transcript peptide (CART); Immunohistochemistry; Levodopa; Parkinson’s disease; Rotational behavior