Drugs acting at cannabinoid type 1 receptors (CB1) have modulatory effects on glutamate and GABA neurotransmission in basal ganglia; thus, they potentially affect motor behavior in the parkinsonian setting. Preclinical trials with diverse cannabinoid agents have shown varied results, and the precise effects of blocking cannabinoid CB1 receptors remain uncertain. We tested behavioral effects of ...

In addition to the medium spiny neurons the mammalian striatum contains a small population of GABAergic interneurons that are immunoreactive for tyrosine hydroxylase (TH), which dramatically increases after lesions to the nigrostriatal pathway and striatal delivery of neurotrophic factors. The regulatory effect of levodopa (L-Dopa) on the number and phenotype of these cells is less well underst...

The present study examined the nature of the apical inward and outward L-3,4-dihydroxyphenylalanine (L-dopa) transporters in LLC-PK(1) cells and whether protein kinases differentially modulate the activities of these transporters. The apical inward transfer of L-dopa was promoted through an energy-dependent and sodium-insensitive transporter (Michaelis constant = 38 microM; maximum velocity = 2...

Rats received intracisternal [(3)H]norepinephrine and, after 5 min, intraperitoneal L-dopa (100 mg/kg); they were killed at intervals during the subsequent 24 hr. Their brains were assayed for norepinephrine, L-dopa, S-adenosylmethionine, and [(3)H]norepinephrine and its metabolites. Rats that received L-dopa had markedly lower brain concentrations of S-adenosylmethionine and of O-methylated me...

Cells of TM10, an established cell line, are melanocytes that contain equal amounts of eumelanin (black pigment) and pheomelanin (yellow pigment). The content of pheomelanin drastically increased when the cells were cultured in growth medium containing 0.2mM-L-dopa (L-dihydroxyphenylalanine), which is the common precursor for both eumelanogenesis and pheomelanogenesis. After this treatment, the...

Following L-DOPA administration, DA metabolites were measured by both in vivo voltammetry and HPLC-ECD. In vivo, the amplitudes of the catechol oxidation currents in both the striatum and frontal cortex increased and reached a plateau from 60 min to 240 min after L-DOPA treatment. L-DOPA, DA, DOPAC and HVA levels measured by HPLC-ECD after L-DOPA treatment were increased in both regions, and th...

The present study examined whether premovement central neural processing in Parkinson's disease was related to functional motor disability and plasma L-dopa concentration. Reaction time (RT) performance in simple and choice RT tasks was assessed while plasma L-dopa levels were controlled by continuous IV L-dopa infusion in five parkinsonian patients. Five age-matched controls performed the same...

The influence of various enzyme inhibitors on the cardiovascular effects of L-dopa (methylester) has been studied to determine the sites of action of the drug or a responsible metabolite. L-Dopa, 10 mg/kg, iv, had minor early effects on heart rate and blood pressure in normal dogs, but in animals with inhibition of monoamine oxidase (MAO), it caused tachycardia and severe hypotension of gradual...

The reduced movement repertoire of Parkinson's disease (PD) is mainly due to degeneration of nigrostriatal dopamine neurons. Restoration of dopamine transmission by levodopa (L-DOPA) relieves motor symptoms of PD but often causes disabling dyskinesias. Subchronic L-DOPA increases levels of adaptor protein p11 (S100A10) in dopaminoceptive neurons of the striatum. Using experimental mouse models ...

BACKGROUND Motor response complications that arise with repeated L-dopa administration for the treatment of Parkinson's disease are well understood but the relationship between motor response complications and affect are not. We proposed that patients with dyskinesias would report rebound worsening in affect during wearing-off of L-dopa effect. METHODS Fifty Parkinson's disease patients with ...