On-line version ISSN 1668-7027
JUSTEL, Nadia; BENTOSELA, Mariana; MUSTACA, Alba and RUETTI, Eliana. Neonatal treatment with clomipramine and depression: A review of behavioral and physiological findings. Interdisciplinaria [online]. 2011, vol.28, n.2, pp. 207-220. ISSN 1668-7027.
Many times in science, the discovery of a treatment that has certain effect happens accidentally while the scientists are investigating another phenomenon. This is the case of the discovery of a possible animal model of depression by the administration of clomipramine (CLI) during neonatal days. Adult animals exposed to CLI in neonatal days showed alterations in REM sleep (for example, the decrease of REM latency); lower weight, disruptions in locomotor activity (the increase in activity depend on the dark / light phase in which the test starts, when the animals were tested in the light phase they found increase in activity, but no changes were observed when the animals were tested in the dark phase); less intracraneal self-stimulation, lower saccharin and sucrose consumption, less suppression of the consummatory behavior, sexual alterations in males (for example, expressed as a lower number of mounts and ejaculations; no alterations were found in the activity of the Hypothalamic - Pituitary - Gonadal axis and the level of testosterone was normal), higher alcohol consumption, disruptions in the agonistic response (CLI - treated animals were significantly less aggressive than control groups) and in learning (in the passive avoidance task and 8 radial arm maze) compared to untreated animals (rats that received vehicle during neonatal days). Several of these abnormalities could be reversed with those treatments that are effective for treating depression in humans (antidepressive drugs, nicotine and REM sleep deprivation treatment). These results were obtained in male rats of different strains and in hamsters, and at different months, the majority of them at 3-4 months, and some of them after the sixth, this could be because some changes were caused with the decrement in the age of the animals, although further research is needed to elucidate this issue. Neuroendocrinal alterations analogous to those found in human depression were also discovered in CLI - treated rats, although the data is contradictory. These include Hypothalamic - Pituitary - Adrenal axis alterations; while it is true that some experimental results found that CLI - treated rats have a higher basal level of corticosterone than controls, others found that not only do they differ in basal level, also during the stress situation; circulating corticosterone increases less and returns more rapidly to basal levels than control groups. For this reason, we can conclude that if alterations in the HPA axis indeed exist in CLI - treated animals, it is still unclear in which way the deregulation is manifested. Other results support the hypothesis that alterations found in CLI - treated animals are due to alterations in serotoninergic transmission during a critical period of development, such as the neonatal stage; more specifically, a reduction in the hypothalamic concentration of serotonin, like a decrease in the neuronal firing in the dorsal raphe nucleus. An increase in cholinergic activity was also found, although the data in this field is not as vast as that found in relation to the neurotransmission of serotonin. All of these results suggest that rats treated with CLI during neonatal days present alterations in adulthood analogous to human depression, however other findings indicate that is not yet a valid model. Further research is needed, and we have to be cautious with the conclusions because there is some evidence suggesting that this is a promising model but other does not support its validity. If a model like the neonatal administration of CLI achieves the reproduction of some symptoms, neurophysiological and behavioral alterations of depression, the advantages are invaluable. In this sense, neonatal treatment with CLI is a very promising animal model for the study of depression.
Keywords : Depression; Clomipramine; Neonatal treatment; Rats.