NMDA antagonist effects on the development of L-dopa behavioral sensitization in rats.
This study, which used an animal model of Parkinsonism, evaluated whether the NMDA antagonist MK-801 can prevent the development of L-3-4-dihydroxyphenylalanine (L-DOPA) sensitization. In separate groups, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were treated with saline, 25 mg/kg L-DOPA methyl ester, 0.1 mg/kg MK-801, or MK-801 plus L-DOPA once per day for 13 days beginning 18 to 20 hr postoperatively, well before the onset of denervation supersensitivity. Following 14 days of withdrawal, all treatment groups were given a saline test and on the next day, an L-DOPA challenge test. Contralateral rotation, the behavioral index of denervation supersensitivity, emerged on Day 7 in both L-DOPA groups. However, on the L-DOPA challenge test, only the L-DOPA group showed enhanced contralateral rotations compared with a drug-naive group. In contrast, the MK-801 and MK-801/L-DOPA groups were indistinguishable from the drug-naive L-DOPA-treated rats. These findings indicate that although MK-801 treatment did not prevent the development of behavioral sensitization to the L-DOPA treatment, it did prevent its persistence following drug withdrawal.
Pinheiro-Carrera
M
M
Department of Psychobiology, University of Sao Paulo, Brazil.
Tomaz
C
C
Huston
J P
JP
Carey
R J
RJ
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000503:physiopathology
D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D016291:Dizocilpine Maleate; D004298:Dopamine