Differences in behavior and monoamine laterality following neonatal clomipramine treatment.
Postnatal treatment between 8 to 21 days of age with clomipramine (15 mg/kg, twice daily) produces an animal model that has many of the behavioral hallmarks of depression. In this study, we investigated the enduring behavioral and neurochemical effects of this early treatment in adult animals. Locomotor activity was increased in clomipramine-treated males, but not females, relative to vehicle-treated subjects. Increases in anxiety-like behavior in the elevated plus maze also were observed in clomipramine-exposed adults, but no sex differences were detected. Clomipramine-treated animals had shifts in the laterality of monoamines in limbic regions with lower serotonin levels on the right side while vehicle-treated animals had lower serotonin on the left side. The lateralization of dopamine content demonstrated the same pattern. This decline in monoaminergic content is consistent with clinical studies demonstrating decrements in serotonin as well as alterations in the lateralization of function in individuals with major depressive order.
Department of Psychiatry, Harvard Medical School, Laboratory of Developmental Psychopharmacology, McLean Hospital, Belmont, MA 02478, USA.
Susan L
SL
Andersen
Nathalie L
NL
Dumont
Martin H
MH
Teicher
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology*; D004298:Dopamine; D005260:Female; D007839:Functional Laterality / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D000929:Antidepressive Agents, Tricyclic; D015306:Biogenic Monoamines; D002997:Clomipramine; D004298:Dopamine