Behavioral tolerance to repeated apomorphine administration in parkinsonian monkeys

J Neurol Sci. 1993 Jan;114(1):40-4. doi: 10.1016/0022-510x(93)90046-2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / analogs & derivatives
  • Animals
  • Apomorphine / pharmacology*
  • Behavior, Animal / drug effects*
  • Dopamine / physiology
  • Dopamine Agents / toxicity
  • Drug Tolerance
  • Female
  • MPTP Poisoning
  • Macaca fascicularis
  • Male
  • Oxazines / pharmacology
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / psychology*
  • Psychomotor Performance / drug effects

Substances

  • Dopamine Agents
  • Oxazines
  • 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine
  • naxagolide
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Apomorphine
  • Dopamine