INVESTIGADORES
TARAVINI Irene Rita Eloisa
artículos
Título:
Cabergoline and pramipexole fail to modify already established dyskinesias in an animal model of parkinsonism.
Autor/es:
LARRAMENDY C; TARAVINI IR; SABORIDO MD; FERRARIO JE; MURER MG; GERSHANIK OS
Revista:
BEHAVIOURAL BRAIN RESEARCH
Editorial:
Elsevier/North-Holland Biomedical Press.
Referencias:
Lugar: Netherlands; Año: 2008
ISSN:
0166-4328
Resumen:
Levodopa-induced dyskinesias are one of the major limiting side effects
encountered in the treatment of Parkinson's disease. Dopamine agonists
of the D2 family are less prone to induce these abnormal involuntary
movements (AIMs), and in some instances it has been proposed that they
could counteract them once already established. As differences in the
plasma half-life of a given DA agonist could be related with a greater
or lesser propensity to induce or to counteract AIMs, we compared the
effects of two D2 agonists (cabergoline and pramipexole) with different
half-lives, and levodopa, at doses producing similar improvement in
purposeful forelimb use, in rats with severe nigrostriatal lesion,
previously sensitized to levodopa. The same therapeutic regime was
subsequently used in pharmacologically naïve rats. We found that: (i)
prior induction of AIMs by levodopa administration primes rats for the
occurrence of AIMs during mono-therapy with pramipexole (but not with
cabergoline); (ii) an intervening period of D2 agonist mono-therapy
does not modify the severity of AIMs induced by subsequent mono-therapy
with levodopa; iii. de novo treatment with D2 agonists is associated
with a lower risk of AIMs (regardless of the severity of the lesion)
and does not modify AIMs during subsequent mono-therapy with levodopa.
An unexpected finding was that prior levodopa therapy sensitized rats
to the therapeutic effects of D2 agonists given in mono-therapy. In
summary, the use of the rat with nigrostriatal lesion to model relevant
therapeutic conditions does not support that D2 agonists prevent the
development of AIMs during subsequent levodopa mono-therapy or can
revert the dysfunction underlying it.