Changes in brain oxidative metabolism induced by inhibitory avoidance learning and acute administration of amitriptyline

• Published in: Pharmacology, biochemistry and behavior Vol. 89; no. 3; pp. 456 - 462
• Main Authors: González-Pardo, Héctor, Conejo, Nélida M., Arias, Jorge L., Monleón, Santiago, Vinader-Caerols, Concepción, Parra, Andrés
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2008; Elsevier Science
• Subjects: Amitriptyline; Amitriptyline - pharmacology; Animals; Antidepressive Agents, Tricyclic - pharmacology; Avoidance Learning - drug effects; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cytochrome oxidase; Electron Transport Complex IV - metabolism; Inhibitory avoidance; Limbic system; Male; Medical sciences; Mice; Mouse; Neuropharmacology; Oxidation-Reduction; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Tricyclic antidepressants; Inhibitory avoidance; Cytochrome oxidase; Amitriptyline; Limbic system; Mouse; Tricyclic antidepressants; Psychotropic; Central nervous system; Cytochrome-c oxidase; Reuptake inhibitor; Encephalon; Learning; Acquisition process; Antidepressant agent; Inhibition; Serotonin; Enzyme; Acute; Rodentia; Catecholamine; Tricyclic compound; Metabolism; Vertebrata; Mammalia; Animal; Neurotransmitter; Norepinephrine; Oxidoreductases; Pharmacokinetics; Avoidance
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2008.01.022

The effects of antidepressant drugs on memory have been somewhat ignored, having been considered a mere side effect of these compounds. However, the memory impairment caused by several antidepressants could be considered to form part of their therapeutic effects. Amitriptyline is currently one of the most prescribed tricyclic antidepressants, and exerts marked anticholinergic and antihistaminergic effects. In this study, we evaluated the effects of inhibitory avoidance (IA) learning and acute administration of amitriptyline on brain oxidative metabolism. Brain oxidative metabolism was measured in several limbic regions using cytochrome oxidase (CO) quantitative histochemistry. Amitriptyline produced a clear impairment in the IA task. In animals exposed only to the apparatus, amitriptyline decreased CO activity in nine brain regions, without affecting the remaining regions. In animals that underwent the IA training phase, amitriptyline reduced CO activity in only three of these nine regions. In animals treated with saline, IA acquisition increased CO activity in the medial prefrontal cortex, the prelimbic cortex, and the medial mammillary body, and diminished it in the medial septum and the nucleus basalis of Meynert with respect to animals exposed only to the IA apparatus. In animals treated with amitriptyline, IA acquisition did not modify CO activity in any of these regions, but increased it in the anteromedial nucleus of the thalamus, the diagonal band of Broca, and the dentate gyrus. The results reveal a pattern of changes in brain oxidative metabolism induced by IA training in saline-treated animals that was clearly absent in animals submitted to the same behavioural training but treated with amitriptyline.