Inter-individual differences in novelty-seeking behavior in rats predict differential responses to desipramine in the forced swim test.
BACKGROUND
Antidepressant medications are effective only in a subpopulation of patients with depression, and some patients respond to certain drugs, but not others. The biological bases for these clinical observations remain unexplained.


OBJECTIVE
To investigate individual differences in response to antidepressants, we have examined the effects of the norepinephrine reuptake inhibitor desipramine (DMI) and the selective serotonin reutake inhibitor fluoxetine (FLU) in the forced swim test (FST) in rats that differ in their emotional behavior.


METHODS
As response to novelty correlates with numerous other measures of emotionality and substance abuse, we contrasted animals that are high responders (HR) in a novel environment with animals that are low responders (LR) and asked whether the two groups exhibit differential responses to DMI (10mg/kg) and FLU (20mg/kg).


RESULTS
At the behavioral level, DMI caused a significant decrease in immobility in LR animals only, while FLU caused a significant reduction in immobility in both groups. Moreover, at the neural level, DMI treatment led to a decrease in FST-induced c-fos messenger RNA levels in medial prefrontal cortex (PFC) and paraventricular nucleus of the hypothalamus (PVN) in LR but not HR animals.


CONCLUSIONS
Taken together, our results suggest that the HR-LR model is a useful tool to investigate individual differences in responses to norepinephrine reuptake inhibitors (NRIs) and that a differential activation of PFC and/or PVN could underlie some of the inter-individual differences in the efficacy of NRIs.
Jama
A
A
St Elizabeths Hospital, 2700 M.L. King Ave SE, Barton Hall, 2nd Floor, Washington, DC 20032, USA.
Cecchi
M
M
Calvo
N
N
Watson
S J
SJ
Akil
H
H
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D003866:Depressive Disorder / Q000523:psychology*; D003891:Desipramine / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D016762:Genes, fos / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D007206:Individuality; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming / Q000523:psychology*
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D012333:RNA, Messenger; D005473:Fluoxetine; D003891:Desipramine; D003345:Corticosterone