Behavioral tolerance to repeated apomorphine administration in parkinsonian monkeys.
Four consecutive injections (s.c.) of apomorphine (Apo) were given to 5 parkinsonian monkeys after i.v. MPTP administration. The minimal effective dose (MED) of Apo was defined as that capable of reducing motor disability by 50% or more for a minimum period of 30 min. Repeated apomorphine injections were given with an interval of 30 min after the motor effect of the previous injection had worn off or with a separation of 3 h between injections. The doses used in different experiments were the MED (2.4 micrograms/kg), 4 MED and 8 MED. In every experiment the duration of motor benefit was longest with the first Apo injection. There was a decay in the duration of the response elicited by consecutive Apo injections when given 30 min after the previous effect had waned. This was significant for the MED and 4 MED (ANOVA, P < 0.01). When Apo boluses were given with an interval of 3 h there was a significant reduction in the duration of the response elicited by the MED, 4 MED and 8 MED of apomorphine. For the MED the reduction in the duration of the motor response was significantly greater for injections given with a 30-min interval than 3-h interval. These findings indicate that behavioral hyposensitivity to repeated Apo administration in parkinsonian monkeys occurs preferentially when near threshold doses are given with short intervals.
Luquin
M R
MR
Department of Neurology, Clinica Universitaria, Pamplona, Spain.
Laguna
J
J
Herrero
M T
MT
Obeso
J A
JA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000633:toxicity; D004361:Drug Tolerance; D005260:Female; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D008297:Male; D010078:Oxazines / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000523:psychology*; D011597:Psychomotor Performance / Q000187:drug effects
D015259:Dopamine Agents; D010078:Oxazines; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; C042631:naxagolide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine; D004298:Dopamine