title: Impramine, fluoxetine and clozapine differently affected reactivity to positive and negative stimuli in a model of motivational anhedonia in rats.
abstract: Anhedonia is a relevant symptom in depression and schizophrenia. Chronic stress exposure induces in rats escape deficit, disrupts the dopaminergic response to palatable food and the competence to acquire sucrose self-administration (SA), thus configuring a possible model of motivational anhedonia. Repeated lithium administration reverts stress effects and brings back to control values the breaking point (BP) score, a measure of reward motivation. In this study, we tested on this model two antidepressants, imipramine and fluoxetine, and two antipsychotics, haloperidol and clozapine. The dopaminergic response to sucrose consumption was studied in non food-deprived rats in terms of dopamine D1 receptor signaling in the nucleus accumbens shell (NAcS). More specifically, we studied the modifications in dopamine and cAMP-regulated phosphoprotein of Mr 32,000 (DARPP-32) phosphorylation pattern following sucrose consumption. Fluoxetine reverted the escape deficit and showed no effects on dopaminergic response and sucrose SA. Imipramine reverted sucrose SA and dopamine response deficit in half of the rats and the escape deficit in all animals. Haloperidol did not affect stress-induced deficits. Clozapine-treated rats recovered the dopaminergic response to sucrose consumption and the competence to acquire sucrose SA, although they still showed the escape deficit, thus confirming that motivation toward reward may be dissociated from that to punishment escape. These results indicate that imipramine or fluoxetine are not endowed with a rapid onset antianhedonic effect. On the other hand, clozapine treatment showed a motivational antianhedonic activity similar to that observed after lithium treatment.
authors: Department of Molecular and Developmental Medicine, University of Siena, Via Moro, 2, 53100 Siena, Italy. Electronic address: scheggi9@unisi.it.
authors: S
authors: S
authors: Scheggi
authors: Department of Molecular and Developmental Medicine, University of Siena, Via Moro, 2, 53100 Siena, Italy. Electronic address: teresapelliccia87@gmail.com.
authors: T
authors: T
authors: Pelliccia
authors: Department of Molecular and Developmental Medicine, University of Siena, Via Moro, 2, 53100 Siena, Italy. Electronic address: alberto.ferrari@unisi.it.
authors: A
authors: A
authors: Ferrari
authors: Department of Molecular and Developmental Medicine, University of Siena, Via Moro, 2, 53100 Siena, Italy. Electronic address: mariagraziella.demontis@unisi.it.
authors: M G
authors: MG
authors: De Montis
authors: Department of Molecular and Developmental Medicine, University of Siena, Via Moro, 2, 53100 Siena, Italy. Electronic address: carla.gambarana@unisi.it.
authors: C
authors: C
authors: Gambarana
mesh_terms: D059445:Anhedonia / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D018020:Lithium Compounds / Q000494:pharmacology; D008297:Male; D009042:Motivation / Q000187:drug effects* / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D019422:Dietary Sucrose; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D018020:Lithium Compounds; C497930:Ppp1r1b protein, rat; D005473:Fluoxetine; D003024:Clozapine; D006220:Haloperidol; D007099:Imipramine; D004298:Dopamine
keywords: dopamine; dopamine and cAMP-regulated phosphoprotein of Mr 32,000 (DARPP-32); self-administration; stress; sucrose