Ketamine-induced hyperlocomotion associated with alteration of presynaptic components of dopamine neurons in the nucleus accumbens of mice

Pharmacol Biochem Behav. 1991 Oct;40(2):399-407. doi: 10.1016/0091-3057(91)90571-i.


The underlying mechanisms of ketamine-induced hyperlocomotion were examined in mice. An intraperitoneal (IP) injection of ketamine (3-150 mg/kg) increased locomotor activity in a dose-dependent fashion. A low dose of ketamine (30 mg/kg) produced peak locomotion within the first 10 min followed by a rapid decline. In contrast, a high dose (150 mg/kg) inhibited locomotor activity to the control level during the first 30 min. Thereafter the activity gradually increased and reached a peak at approximately 2 h followed by a gradual decline. The hyperactivities induced by both low and high doses of ketamine were inhibited by a low dose of haloperidol (0.10 mg/kg, IP), a dopamine (DA) receptor antagonist. However, neither a high dose of phenoxybenzamine (10 mg/kg, IP), an alpha-blocker nor a high dose of propranolol (20 mg/kg, IP), a beta-blocker inhibited the hyperactivities. Destruction of catecholaminergic terminals by 6-hydroxydopamine suppressed ketamine-induced hyperlocomotion. Regional brain monoamine assays revealed that, at peak locomotion, a low dose of ketamine (30 mg/kg) selectively increased DA turnover in the nucleus accumbens which is a forebrain region believed to be involved in the initiation and regulation of locomotor activity, while a high dose (150 mg/kg) increased not only DA but also norepinephrine and serotonin turnover in many regions of the brain. In vitro, ketamine slightly provoked [3H]DA release from nucleus accumbens and striatal slices to a similar extent, but inhibited synaptosomal uptake of [3H]DA in the nucleus accumbens to a greater degree than in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Anesthesia
  • Animals
  • Biogenic Monoamines / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / physiology*
  • Haloperidol / pharmacology
  • Ketamine / pharmacology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Motor Activity / drug effects*
  • Neurons / drug effects
  • Neurons / physiology*
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology*
  • Oxidopamine / pharmacology
  • Phenoxybenzamine / pharmacology
  • Propranolol / pharmacology
  • Synapses / drug effects*


  • Biogenic Monoamines
  • Phenoxybenzamine
  • Ketamine
  • Oxidopamine
  • Propranolol
  • Haloperidol
  • Dopamine