Destruction of the locus coeruleus or the dorsal NE bundle does not alter the release of punished responding by ethanol and chlordiazepoxide

The hypothetical involvement of central noradrenergic projections in the manifestation of "anxiety" and the "anti-anxiety" effects of alcohol and benzodiazepines was tested in an operant conflict situation by examining the effects of destruction of this noradrenergic system on response rates. Rats were trained on a Geller-Seifter conflict test [9] modified for incremental shock [21], in which two food-reinforced lever press components were separated by a time-out. Responses during the "food-alone" component (RI) were reinforced on a random interval schedule-30 sec; responses during the "time-out" component were never reinforced; and responses during the conflict component (CONFLICT) were continuously reinforced with both food and shock. This shock strength increased incrementally with each successive shock during the conflict period. Each session consisted of two cycles of a 5 min RI period, a two min time out, and a two min CONFLICT period presented in succession. Both ethanol (0.5 to 1.0 g/kg) and chlordiazepoxide (5 and 10 mg/kg) produced a significant increase in punished responding during the CONFLICT component. Ethanol, but not chlordiazepoxide (CDP) also significantly decreased responding during the RI component. Virtual total destruction of the dorsal noradrenergic projection with 6-hydroxydopamine (6-OHDA), or destruction of the locus coeruleus itself, failed to significantly alter baseline responding or the release of punished responding to ethanol or CDP. These results do not support the hypothesis that the locus coeruleus projections have an essential role in "anxiety" or in the "anxiety-reducing" properties of ethanol or the benzodiazepines.

[1]  G. Koob,et al.  Brain norepinephrine depleting lesions selectively enhance behavioral responsiveness to novelty , 1984, Physiology & Behavior.

[2]  G. Koob,et al.  Locus coeruleus lesions and learning in the rat , 1976, Physiology & Behavior.

[3]  F. Bloom,et al.  Nonrepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  D. R. Snyder,et al.  Behavioral effects of stimulation of the nucleus locus coeruleus in the stump-tailed monkeyMacaca arctoides , 1976, Brain Research.

[5]  S. T. Mason,et al.  Noradrenaline and neophobia , 1978, Physiology & Behavior.

[6]  D E Redmond,et al.  Current concepts. II. New evidence for a locus coeruleus-norepinephrine connection with anxiety. , 1979, Life sciences.

[7]  D. R. Britton,et al.  A sensitive open field measure of anxiolytic drug activity , 1981, Pharmacology Biochemistry and Behavior.

[8]  D. Roberts,et al.  Failure to replicate the dorsal bundle extinction effect: Telencephalic norepinephrine depletion does not reliably increase resistance to extinction but does augment gustatory neophobia , 1983, Brain Research.

[9]  L. Cook,et al.  Behavioral analysis of the effects and mechanisms of action of benzodiazepines. , 1975, Advances in biochemical psychopharmacology.

[10]  S. T. Mason,et al.  Locus coeruleus lesions: Learning and extinction , 1978, Physiology & Behavior.

[11]  P. Kelly,et al.  Effect of minor tranquillisers on hippocampal θ rhythm mimicked by depletion of forebrain noradrenaline , 1975, Nature.

[12]  Redmond De Clonidine and the primate locus coeruleus: evidence suggesting anxiolytic and anti-withdrawal effects. , 1981 .

[13]  S. T. Mason,et al.  Noradrenaline and selective attention: a review of the model and the evidence. , 1980, Life sciences.

[14]  S. T. Mason,et al.  Altered exploratory behaviour after 6-OHDA lesion to the dorsal noradrenergic bundle , 1977, Nature.

[15]  F. Bloom,et al.  The action of norepinephrine in the rat hippocampus. III. Hippocampal cellular responses to locus coeruleus stimulation in the awake rat , 1976, Brain Research.

[16]  R. Roth,et al.  The determination of a brain arteriovenous difference for 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) , 1976, Brain Research.

[17]  B. J. Winer Statistical Principles in Experimental Design , 1992 .

[18]  M. Lader The peripheral and central role of the catecholamines in the mechanisms of anxiety. , 1974, International pharmacopsychiatry.

[19]  J. Gray,et al.  Précis of The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system , 1982, Behavioral and Brain Sciences.

[20]  G. Koob,et al.  Dissociation of hyperdipsia from the destruction of the locus coeruleus in rats , 1976, Brain Research.