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A Single Exposure to Morphine Induces Long‐Lasting Hyporeactivity of Rat Caudate Putamen Dopaminergic Nerve Terminals
Author(s) -
PEREIRA FREDERICO C.,
SANTOS SANDRA D.,
RIBEIRO CARLOS F.,
ALI SYED F.,
MACEDO TICE R.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1316.051
Subject(s) - neurochemical , morphine , dopaminergic , putamen , chemistry , dopamine , medicine , endocrinology , caudate nucleus , opioid , pharmacology , anesthesia , receptor
A bstract : The long‐lasting effects of exposure to drugs of abuse on the brain is a central theme in drug addiction research. This study was designed to evaluate whether enduring neurochemical adaptations within caudate putamen can be evoked by a single injection of a high dose of morphine. Rats were pretreated once with 10 mg/kg morphine. Seven days later the effect of another injection of 10 mg/kg morphine on total levels of dopamine (DA), 3,4‐dihydroxyphenylacetic acid (DOPAC), and homovanilic acid (HVA) in caudate putamen was assessed in half the pretreated animals. An irreversible μ‐opioid receptor antagonist, cloccinamox (C‐CAM; 0.1 mg/kg), significantly antagonized the elevation of the HVA/DA ratio, but not the elevation of the DOPAC/DA ratio induced by morphine in the caudate putamen from drug‐naive animals. Pretreatment with morphine blunted changes in the HVA/DA ratio induced by another morphine challenge, but it had no effect on the DOPAC/DA ratio within the caudate putamen. Therefore, a single dose of 10 mg/kg morphine hampered nigrostriatal DA release and extraneuronal metabolism, μ‐opioid receptor mediated, on another 10 mg/kg morphine challenge. This confirms that the first exposure to morphine does not go without long‐lasting neurochemical adaptations.