Dose-dependent opposite effects of nortriptyline on affective-like behavior in adolescent rats: Comparison with adult rats
European Journal of Pharmacology. 2021-11-01; 910: 174465
DOI: 10.1016/j.ejphar.2021.174465
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Bis-Humbert C(1), García-Cabrerizo R(1), García-Fuster MJ(2).
Author information:
(1)IUNICS, University of the Balearic Islands, Palma, Spain; Health Research
Institute of the Balearic Islands (IdISBa), Palma, Spain.
(2)IUNICS, University of the Balearic Islands, Palma, Spain; Health Research
Institute of the Balearic Islands (IdISBa), Palma, Spain. Electronic address:
.
Antidepressant drugs elicit different behavioral and neurochemical responses
with age. In fact, the use of antidepressants during adolescence is associated
with an increased risk of suicidal thinking, being the best pharmacological
treatment during this critical period a matter of constant debate in terms of
its risk-benefit outcome. In this regard, the present study compared the effects
of nortriptyline (3-10 mg/kg, 7 days) on regulating different aspects of
affective-like behavior by screening adolescent and adult Sprague-Dawley rats
through several consecutive tests (forced-swim, open field, sucrose preference).
Brains were later collected to evaluate hippocampal neurogenesis and mBDNF
protein content as potential molecular correlates of the observed behavioral
responses. The main results in adolescent rats showed that nortriptyline induced
dose-dependent opposite effects: while 3 mg/kg decreased immobility and
increased mBDNF (indicative of an antidepressant-like response), 10 mg/kg
decreased exploratory time in the open field and mBDNF (suggestive of an
anxiogenic-like response). These effects were not associated with changes in
neurogenesis regulation. In adult rats, nortriptyline failed to modulate
affective-like behavior or the neuroplasticity markers evaluated at the doses
tested. In conclusion, clear behavioral and neurochemical differences were
observed between adolescent and adult rats in response to nortriptyline
treatment. Interestingly, while nortriptyline displayed an antidepressant-like
potential at the lowest dose examined in adolescence, a higher dose shifted
these results towards a negative outcome, thus reinforcing the need to extreme
caution when considering this treatment for our younger population.
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.