Chronic treatment with imipramine reverses immobility behaviour, hippocampal corticosteroid receptors and cortical 5-HT(1A) receptor mRNA in prenatally stressed rats.
Prenatal stress in the rat induces enhanced reactivity of the hypothalamus-pituitary-adrenal (HPA) axis, disturbances in a variety of circadian rhythms and increased anxiety-like behaviour. Such abnormalities parallel those found in human depressed patients. Prenatally stressed (PS) rats could represent, therefore, an interesting animal model for the evaluation of the efficacy of pharmacotherapeutic intervention in psychiatric disorders that has often been addressed using control animals. In the present study, PS and non-stressed rats were chronically treated with the tricyclic antidepressant imipramine (10 mg/kg i.p. for 21 days) and assessed in the forced swim test. Glucocorticoid receptor binding sites in the hippocampus were measured and 5-HT(1A) receptor mRNA levels in the frontal cortex were also assessed. PS rats were characterised by increased immobility in the forced swim test, reduced hippocampal corticosteroid receptor binding and increased levels of cortical 5-HT(1A) mRNA. All these parameters were significantly reversed by chronic imipramine treatment. Conversely, no significant effects were observed for non-stressed rats. All these effects are consistent with the expected pharmacotherapy of depression-like abnormalities in PS rats. These results further indicate that PS rats are a relevant animal model of depression.
Morley-Fletcher
S
S
Laboratory of Perinatal Stress JE2365, University of Lille 1, Bt. SN4.1, 59655, Villeneuve d'Ascq, France.
Darnaudéry
M
M
Mocaer
E
E
Froger
N
N
Lanfumey
L
L
Laviola
G
G
Casolini
P
P
Zuena
A R
AR
Marzano
Lorenzo
L
Hamon
M
M
Maccari
S
S
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000523:psychology*; D013550:Swimming / Q000523:psychology
D000929:Antidepressive Agents, Tricyclic; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D044282:Receptor, Serotonin, 5-HT1A; D007099:Imipramine