Excessive @entity2227 transmission in the basal ganglia is a major factor in the neural mechanisms underlying @entity191 . Activation of kappa opioid receptors causes a presynaptic reduction in @entity2227 release. Kappa opioid receptors are concentrated in those regions of the basal ganglia associated with increased @entity2227 transmission in @entity304 . In this study, we use the @entity8490 and @entity2515 -treated @entity35 model of @entity304 to investigate whether systemic administration of the kappa opioid agonists @entity31408 (CI-977) and U69,593 can alleviate the symptoms of @entity304 either alone or in conjunction with @entity935 replacement therapy. We report that, when administered alone, both @entity31408 and U69,593 can increase locomotion in @entity1154 -depleted @entity35 . No @entity2915 was seen after kappa opioid agonist administration in non-parkinsonian @entity35 . The responses to kappa opioid agonists were blocked by co-administration of either the nonspecific opioid receptor antagonist @entity1510 or the selective kappa opioid receptor antagonist @entity14719 ( @entity14719 ). An important finding is that when @entity31408 and L-dopa are administered together, their anti- @entity2845 properties are synergistic. Thus, the doses of @entity31408 and L-dopa required to alleviate @entity910 when administered together are lower than either administered alone. These data illustrate the importance of kappa opioid receptors in the neural mechanisms controlling @entity717 and suggest that kappa opioid agonists may have a role as adjuncts to @entity935 replacement in the management of @entity191 .

Kappa-opioid receptor agonists increase locomotor activity in the @entity1154 -depleted XXXX model of @entity304 .

@entity2227 :: ('CHEBI:29987', 'Chemical') :: ['glutamate'] @entity304 :: ('MESH:D010302', 'Disease') :: ['parkinsonism'] @entity2515 :: ('MESH:D012110', 'Chemical') :: ['reserpine'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity910 :: ('MESH:D004409', 'Disease') :: ['akinesia'] @entity191 :: ('MESH:D010300', 'Disease') :: ['parkinsonian akinesia', "Parkinson's disease"] @entity31408 :: ('MESH:C067110', 'Chemical') :: ['enadoline'] @entity1510 :: ('MESH:D009270', 'Chemical') :: ['naloxone'] @entity14719 :: ('MESH:C051844', 'Chemical') :: ['nor-BNI', 'nor-binaltorphimine'] @entity2915 :: ('MESH:D006948', 'Disease') :: ['increase in locomotor activity'] @entity2845 :: ('MESH:D018476', 'Disease') :: ['akinetic'] @entity8490 :: ('CHEBI:6912', 'Chemical') :: ['alpha-methyl-p-tyrosine'] @entity1154 :: ('CHEBI:25375', 'Chemical') :: ['monoamine'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity717 :: ('MESH:D009069', 'Disease') :: ['voluntary movement']
@entity35 :: (10116,Species) :: ['rat']
