Further evidence for an immediate antidepressant action of intracerebral drug administration in a model of chronic depression.
This study was designed to replicate an earlier finding of a rapid acute therapeutic action of intracerebrally administered antidepressant in chronically depressed rodents. The effects of acute fourth ventricular (ivt.) injections were compared to those of acute peripheral (i.p.) injections of desipramine (DMI) in mice subjected to repeated open-space forced swim. In confirmation, it was found that a single ivt. injection of a low (3 nmol) but not high (30 nmol) dose immediately reversed the immobility and inactivity of the model whereas acute i.p. administration was without effect up to 30 mg/kg. The repeated forced swim stress was also found to significantly reduce the net accumulation of DMI in the brain but not liver after a single i.p. injection of a moderate dose (10 mg/kg). The results suggest that stress-induced alterations of regional drug uptake or metabolism in the CNS may contribute to the therapeutic lag for antidepressants and other compounds in disorders with high distress.
Lin
Yan
Y
New York University Langone School of Medicine, Department of Psychiatry, 550 First Ave, New York, NY, USA.
Suckow
Raymond F
RF
Sarfraz
Yasmeen
Y
Stone
Eric A
EA
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D003863:Depression / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy*; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007267:Injections; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013550:Swimming; D013997:Time Factors
D000928:Antidepressive Agents; D003891:Desipramine