INVESTIGADORES
TARAVINI Irene Rita Eloisa
artículos
Título:
Mapping the effects of three dopamine agonists with different dyskinetogenic potential and receptor selectivity using pharmacological functional magnetic resonance imaging.
Autor/es:
DELFINO MA; KALISCH R; CZISCH M; LARRAMENDY C; RICATTI J; TARAVINI IR; TRENKWALDER C; MURER MG; AUER DP; GERSHANIK OS
Revista:
NEUROPSYCHOPHARMACOLOGY
Editorial:
Nature Publishing Group
Referencias:
Lugar: United States; Año: 2007 vol. 32 p. 1911 - 1921
ISSN:
0893-133X
Resumen:
The mechanisms underlying dopamine agonist-induced dyskinesia in
Parkinson's disease remain poorly understood. Similar to patients, rats
with severe nigrostriatal degeneration induced by 6-hydroxydopamine are
more likely to show dyskinesia during chronic treatment with
unselective dopamine receptor agonists than with D2 agonists,
suggesting that D1 receptor stimulation alone or in conjunction with D2
receptor stimulation increases the chances of experiencing dyskinesia.
As a first step towards disclosing drug-induced brain activation in
dyskinesia, we examined the effects of dopamine agonists on behavior
and blood oxygenation level-dependent (BOLD) signal in the striatum and
motor cortex of rats with unilateral nigrostriatal lesions. Rats were
rendered dyskinetic before pharmacologic functional magnetic resonance
imaging by means of a repeated treatment regime with dopamine agonists.
The unselective agonist apomorphine and the selective D1/D5 agonist
SKF-81297 induced strong forelimb dyskinesia (FD) and axial dystonia
and increased BOLD signal in the denervated striatum. Besides,
SKF-81297 produced a significant but smaller BOLD increase in the
intact striatum and a symmetric bilateral increase in the motor cortex.
The D2 family agonist quinpirole, which induced mild dyskinesia on
chronic treatment, did not produce BOLD changes in the striatum or
motor cortex. Further evidence to support an association between BOLD
changes and dyskinesia comes from a direct correlation between scores
of FD and magnitude of drug-induced BOLD increases in the denervated
striatum and motor cortex. Our results suggest that striatal and
cortical activation induced by stimulation of D1/D5 receptors has a
primary role in the induction of peak dose dyskinesia in parkinsonism.