A single exposure to morphine induces long-lasting hyporeactivity of rat caudate putamen dopaminergic nerve terminals.
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 mu-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, mu-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.
Pereira
Frederico C
FC
Instituto de Farmacologia e Terapêutica, Medical School, University of Coimbra, Coimbra, Portugal. fredcp@ci.uc.pt
Santos
Sandra D
SD
Ribeiro
Carlos F
CF
Ali
Syed F
SF
Macedo
Tice R
TR
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006948:Hyperkinesis / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009020:Morphine; D004298:Dopamine