Hyperactivity in neonatally dopamine-lesioned rats requires residual activity in mesolimbic dopamine neurons

Pharmacol Biochem Behav. 1995 May;51(1):159-63. doi: 10.1016/0091-3057(94)00335-g.

Abstract

Neonatal destruction of mesencephalic dopamine (DA) neurons in rats through administration of 6-hydroxydopamine (6-OHDA; 75 micrograms IC) leads to locomotor hyperactivity at adulthood. Treatment with the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (H44/68; 250 mg/kg) was shown to reduce the motor activity of neonatally 6-OHDA-lesioned rats to activity levels similar to controls. In both animal groups, DA and metabolite tissue levels decreased after the H44/68 treatment. However, the extent of the H44/68-induced DA decrease was less pronounced in the 6-OHDA-lesioned animals, with no change at all in the dorsal striatum. These results imply that residual activity in mesolimbic DA neurons is required for maintaining the hyperactivity seen after neonatal 6-OHDA lesions, and that this hyperactivity is apparently mediated by postsynaptic alterations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / physiology*
  • Biogenic Monoamines / metabolism
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Limbic System / drug effects
  • Limbic System / metabolism
  • Limbic System / physiology*
  • Male
  • Methyltyrosines / pharmacology
  • Motor Activity / drug effects*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Oxidopamine
  • Rats
  • Rats, Sprague-Dawley
  • Stimulation, Chemical
  • Tyrosine 3-Monooxygenase / antagonists & inhibitors
  • alpha-Methyltyrosine

Substances

  • Biogenic Monoamines
  • Methyltyrosines
  • alpha-Methyltyrosine
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Dopamine