Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine. 1994

M Papp, and V Klimek, and P Willner
Institute of Pharmacology, Polish Academy of Sciences, Krakow.

Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2-receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1-receptors.

UI MeSH Term Description Entries
D007099 Imipramine The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. Imidobenzyle,Imizin,4,4'-Methylenebis(3-hydroxy-2-naphthoic acid)-3-(10,11-dihydro-5H-dibenzo(b,f)azepin-5-yl)-N,N-dimethyl-1-propanamine (1:2),Imipramine Hydrochloride,Imipramine Monohydrochloride,Imipramine Pamoate,Janimine,Melipramine,Norchlorimipramine,Pryleugan,Tofranil
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008032 Limbic System A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the AMYGDALA; EPITHALAMUS; GYRUS CINGULI; hippocampal formation (see HIPPOCAMPUS); HYPOTHALAMUS; PARAHIPPOCAMPAL GYRUS; SEPTAL NUCLEI; anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). Limbic Systems,System, Limbic,Systems, Limbic
D008297 Male Males
D004435 Eating The consumption of edible substances. Dietary Intake,Feed Intake,Food Intake,Macronutrient Intake,Micronutrient Intake,Nutrient Intake,Nutritional Intake,Ingestion,Dietary Intakes,Feed Intakes,Intake, Dietary,Intake, Feed,Intake, Food,Intake, Macronutrient,Intake, Micronutrient,Intake, Nutrient,Intake, Nutritional,Macronutrient Intakes,Micronutrient Intakes,Nutrient Intakes,Nutritional Intakes
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013315 Stress, Psychological Stress wherein emotional factors predominate. Cumulative Stress, Psychological,Emotional Stress,Individual Stressors,Life Stress,Psychological Cumulative Stress,Psychological Stress Experience,Psychological Stress Overload,Psychologically Stressful Conditions,Stress Experience, Psychological,Stress Measurement, Psychological,Stress Overload, Psychological,Stress Processes, Psychological,Stress, Emotional,Stressful Conditions, Psychological,Psychological Stress,Stress, Psychologic,Stressor, Psychological,Condition, Psychological Stressful,Condition, Psychologically Stressful,Conditions, Psychologically Stressful,Cumulative Stresses, Psychological,Experience, Psychological Stress,Individual Stressor,Life Stresses,Measurement, Psychological Stress,Overload, Psychological Stress,Psychologic Stress,Psychological Cumulative Stresses,Psychological Stress Experiences,Psychological Stress Measurement,Psychological Stress Measurements,Psychological Stress Overloads,Psychological Stress Processe,Psychological Stress Processes,Psychological Stresses,Psychological Stressful Condition,Psychological Stressful Conditions,Psychological Stressor,Psychological Stressors,Psychologically Stressful Condition,Stress Experiences, Psychological,Stress Processe, Psychological,Stress, Life,Stress, Psychological Cumulative,Stressful Condition, Psychological,Stressful Condition, Psychologically,Stressor, Individual
D013395 Sucrose A nonreducing disaccharide composed of GLUCOSE and FRUCTOSE linked via their anomeric carbons. It is obtained commercially from SUGARCANE, sugar beet (BETA VULGARIS), and other plants and used extensively as a food and a sweetener. Saccharose
D016548 Prosencephalon The anterior of the three primitive cerebral vesicles of the embryonic brain arising from the NEURAL TUBE. It subdivides to form DIENCEPHALON and TELENCEPHALON. (Stedmans Medical Dictionary, 27th ed) Forebrain,Forebrains
D017072 Neostriatum The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.

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