Behavioural and neurochemical effects induced by chronic mild stress applied to two different rat strains.
Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in rats that resembles some of the symptoms of endogenous depression in humans. In the present study, CMS-induced behavioural responses along with neurochemical alterations in dopaminergic and serotonergic function in prefrontal cortex, striatum, hypothalamus and hippocampus were examined following treatment with imipramine in Wistar and Sprague-Dawley rats. The CMS procedure lasted 7 weeks in total. Once per week, a 1-h preference test for 1% sucrose solution was conducted. Treatment with imipramine (10mg/kg i.p., once daily) commenced after experimental week 3. CMS induced significant reductions in absolute and relative sucrose intake and sucrose preference in both rat strains but their temporal pattern was different especially during the weeks 0-3. These effects were reversed by IMI. An increase in the dopaminergic and a decrease in the serotonergic activity were observed in the prefrontal cortex in both rat strains following CMS. A decrease in the striatal dopaminergic activity and an increased hippocampal serotonergic activity were also seen in both rat strains following CMS. In Wistar rats, dopaminergic and serotonergic activities were enhanced in the hypothalamus whereas in Sprague-Dawley rats no such stress-induced changes were observed. Notably, the clear decrease in sucrose consumption observed in stressed Wistar rats could be directly associated with a respective increase in the dopaminergic hypothalamic activity. Chronic treatment with imipramine normalized all neurochemical alterations induced by CMS. Our results suggest that a specific and regionally differentiated serotonin-dopamine interaction is directly related to the observed stress-induced anhedonia.
Bekris
Stathis
S
Department of Experimental Pharmacology, Medical School, University of Athens, M. Asias 75, Goudi, 11527 Athens, Greece.
Antoniou
Katerina
K
Daskas
Spyros
S
Papadopoulou-Daifoti
Zeta
Z
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002908:Chronic Disease; D004298:Dopamine / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology; D005518:Food Preferences / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007099:Imipramine / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013395:Sucrose; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D013395:Sucrose; D007099:Imipramine; D004298:Dopamine; D006719:Homovanillic Acid