Behavioral and biochemical effect of chronic treatment with D-1 and/or D-2 dopamine agonists in MPTP monkeys. 1988

P Falardeau, and S Bouchard, and P J Bédard, and R Boucher, and T Di Paolo
School of Pharmacy, Laval University, Québec, Canada.

Monkeys developed a severe parkinsonian syndrome after intravenous administration of (MPTP). L-DOPA/carbidopa (D-1 and D-2) or bromocriptine (D-2) treatment relieved the parkinsonian symptoms, whereas SKF 38393 (D-1) was ineffective. No dyskinesia was seen in monkeys receiving bromocriptine or SKF 38393 as opposed to the L-DOPA-treated animals, in which the dyskinetic response appeared to increased with time. MPTP induced a significant increase (25%, P less than 0.01) in the number of [3H]spiperone binding sites (Bmax) in the caudate nucleus and in putamen. The Bmax of spiperone binding in the L-DOPA-treated monkeys was on average 18% lower (P less than 0.01) than that of the animals treated with MPTP alone. The Bmax for the bromocriptine-treated group was 29% (P less than 0.01) less than that in the MPTP-treated group or 11% (P less than 0.05) less than that in the L-DOPA-treated monkeys. The SKF 38393 treatment induced a 23% (P less than 0.01) decrease in the Bmax as compared to that of animals treated with MPTP alone, and no significant change compared to the L-DOPA- or bromocriptine-treated animals. These results suggest that stimulation of D-1 and D-2 dopamine receptors can differently influence the mechanisms controlling dopamine agonist-induced dyskinesia in MPTP-treated monkeys.

UI MeSH Term Description Entries
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D010302 Parkinson Disease, Secondary Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42) Atherosclerotic Parkinsonism,Secondary Parkinsonism,Symptomatic Parkinson Disease,Parkinson Disease, Secondary Vascular,Parkinson Disease, Symptomatic,Parkinsonism, Secondary,Parkinsonism, Symptomatic,Secondary Vascular Parkinson Disease,Parkinsonism, Atherosclerotic,Secondary Parkinson Disease,Symptomatic Parkinsonism
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004409 Dyskinesia, Drug-Induced Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199) Dyskinesia, Medication-Induced,Medication-Induced Dyskinesia,Drug-Induced Dyskinesia,Drug-Induced Dyskinesias,Dyskinesia, Drug Induced,Dyskinesia, Medication Induced,Dyskinesias, Drug-Induced,Dyskinesias, Medication-Induced,Medication Induced Dyskinesia,Medication-Induced Dyskinesias
D005260 Female Females
D006719 Homovanillic Acid A 3-O-methyl ETHER of (3,4-dihydroxyphenyl)acetic acid. 3-Methoxy-4-Hydroxyphenylacetic Acid,4-Hydroxy-3-Methoxyphenylacetic Acid,3 Methoxy 4 Hydroxyphenylacetic Acid,4 Hydroxy 3 Methoxyphenylacetic Acid,Acid, 3-Methoxy-4-Hydroxyphenylacetic,Acid, 4-Hydroxy-3-Methoxyphenylacetic,Acid, Homovanillic

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