Effects of clonidine in the locus coeruleus on prefrontal- and hippocampal-dependent measures of attention and memory in the rat.

Academic Article


  • RATIONALE: The locus coeruleus (LC) is the source of norepinephrine (NE) in the prefrontal cortex (PFC) and hippocampus and may influence cognitive functions of these areas. Chronic effects of LC-NE lesions do not correspond consistently with acute effects of systemic or intracortical injections of adrenergic agents. OBJECTIVE: These studies aim to manipulate LC activity pharmacologically and study acute effects on measures of attention and memory that depend on the PFC and hippocampus. METHODS: Rats were trained to criterion for one of three tasks: visuospatial reaction time (VSRT), a measure of attention sensitive to PFC lesions, delayed matching trained with retractable levers (DM-RL), and delayed nonmatching trained in radial mazes (DNM-RM), measures of spatial working memory sensitive to PFC and hippocampal lesions, respectively. LC activity was manipulated with bilateral 0.5-microl injections of the alpha-2 agonist clonidine (0, 1.1, 4.5, and 18 nmol). RESULTS: Clonidine produced significant dose-dependent impairments of VSRT, affecting choice response time at the 18-nmol dose and choice accuracy at the 4.5- and 18-nmol doses. Clonidine had no effect on DMRL or DNM-RM at any of the doses tested. CONCLUSIONS: Reversible reduction of LC-NE activity by clonidine impaired measures of visuospatial attention sensitive to PFC lesions but were insufficient to affect PFC- or hippocampal-dependent measures of spatial working memory. These results are consistent with reports that LC-NE lesions produce chronic deficits in attention with little or no effect on measures of working memory.
  • Authors

  • Mair, Robert D
  • Zhang, Yueping
  • Bailey, Kathleen R
  • Toupin, Margaret M
  • Mair, Robert
  • Status

    Publication Date

  • September 2005
  • Published In

  • Psychopharmacology  Journal
  • Keywords

  • Analgesics
  • Animals
  • Attention
  • Behavior, Animal
  • Clonidine
  • Dose-Response Relationship, Drug
  • Hippocampus
  • Locus Coeruleus
  • Male
  • Maze Learning
  • Memory
  • Microinjections
  • Norepinephrine
  • Photomicrography
  • Prefrontal Cortex
  • Rats
  • Rats, Long-Evans
  • Reaction Time
  • Stereotaxic Techniques
  • Digital Object Identifier (doi)

    Pubmed Id

  • 15830223
  • Start Page

  • 280
  • End Page

  • 288
  • Volume

  • 181
  • Issue

  • 2