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.
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: J J Hagan; R A Leslie; S Patel; M L Evans; T A Wattam; S Holmes; C D Benham; S G Taylor; C Routledge; P Hemmati; R P Munton; T E Ashmeade; A S Shah; J P Hatcher; P D Hatcher; D N Jones; M I Smith; D C Piper; A J Hunter; R A Porter; N Upton Journal: Proc Natl Acad Sci U S A Date: 1999-09-14 Impact factor: 11.205
Authors: Tommy Pattij; Dustin Schetters; Anton N M Schoffelmeer; Marcel M van Gaalen Journal: Psychopharmacology (Berl) Date: 2011-07-19 Impact factor: 4.530
Authors: John O'Donnell; Douglas Zeppenfeld; Evan McConnell; Salvador Pena; Maiken Nedergaard Journal: Neurochem Res Date: 2012-06-21 Impact factor: 3.996
Authors: Dardo Tomasi; Rita Z Goldstein; Frank Telang; Thomas Maloney; Nelly Alia-Klein; Elisabeth C Caparelli; Nora D Volkow Journal: Psychiatry Res Date: 2007-06-19 Impact factor: 3.222
Authors: Jean A Milstein; Olivia Lehmann; David E H Theobald; Jeffrey W Dalley; Trevor W Robbins Journal: Psychopharmacology (Berl) Date: 2006-11-10 Impact factor: 4.530
Authors: Dong-Oh Seo; Eric T Zhang; Sean C Piantadosi; David J Marcus; Laura E Motard; Bryce K Kan; Adrian M Gomez; Tammy K Nguyen; Li Xia; Michael R Bruchas Journal: Neuron Date: 2021-06-02 Impact factor: 18.688