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Methylphenidate alters basal ganglia neurotensin systems through dopaminergic mechanisms: a comparison with cocaine treatment
Author(s) -
Alburges Mario E.,
Hoonakker Amanda J.,
Horner Kristen A.,
Fleckenstein Annette E.,
Hanson Glen R.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07215.x
Subject(s) - nucleus accumbens , ventral tegmental area , dopamine , basal ganglia , medicine , endocrinology , striatum , dopaminergic , neurotensin , substantia nigra , globus pallidus , chemistry , neuropeptide , central nervous system , receptor
J. Neurochem. (2011) 117 , 470–478. Abstract Methylphenidate (MPD) is a psychostimulant widely used to treat behavioral problems such as attention deficit hyperactivity disorder. MPD competitively inhibits the dopamine (DA) transporter. Previous studies demonstrated that stimulants of abuse, such as cocaine (COC) and methamphetamine differentially alter rat brain neurotensin (NT) systems through DA mechanisms. As NT is a neuropeptide primarily associated with the regulation of the nigrostriatal and mesolimbic DA systems, the effect of MPD on NT‐like immunoreactivity (NTLI) content in several basal ganglia regions was assessed. MPD, at doses of 2.0 or 10.0 mg/kg, s.c., significantly increased the NTLI contents in dorsal striatum, substantia nigra and globus pallidus; similar increases in NTLI were observed in these areas after administration of COC (30.0 mg/kg, i.p.). No changes in NTLI occurred within the nucleus accumbens, frontal cortex and ventral tegmental area following MPD treatment. In addition, the NTLI changes in basal ganglia regions induced by MPD were prevented when D 1 (SCH 23390) or D 2 (eticlopride) receptor antagonists were coadministered with MPD. MPD treatment also increased dynorphin (DYN) levels in basal ganglia structures. These findings provide evidence that basal ganglia, but not limbic, NT systems are significantly affected by MPD through D 1 and D 2 receptor mechanisms, and these NTLI changes are similar, but not identical to those which occurred with COC administration. In addition, the MPD effects on NT systems are mechanistically distinct from the effects of methamphetamine.