Inter-individual differences in novelty-seeking behavior in rats predict differential responses to desipramine in the forced swim test

摘要

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. 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 for their emotional behavior. After FST, animals with higher locomotor activity in a novel environment (HR) showed higher c-fos mRNA levels than their counterpart (LR) in the locus coeruleus (LC). No group differences in c-fos mRNA expression were present in the dorsal raphe nucleus or nucleus of the solitary tract (NTS). When behavioral effects of DMI or FLU were compared in HR vs. LR animals in the FST, DMI caused a significant decrease in immobility in LR animals only, while FLU caused a significant reduction in immobility regardless of the animals’ phenotype. Moreover, our results showed a decrease in FST-induced c-fos mRNA levels in prefrontal cortex (PFC) and paraventricular nucleus of the hypothalamus (PVN) in LR but not HR animals after DMI treatment, and a significant decrease in FST-induced corticosterone secretion in DMI-treated LR but not HR rats. Taken together, our results suggest that the HR-LR model is a useful tool to investigate individual differences in responses to norepinephrine reutake inhibitors (NRIs) and that a diffential activation of PFC and/or PVN could underlie some of the inter-individual differences in NRIs efficacy.