Modelling early life exposure to antidepressants in rats: Developmental, behavioural and neurochemical aspects
Date
2013-02-11Author
O'Brien, Sandra
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Abstract
Depression during pregnancy and the postpartum period has been associated with
deleterious consequences such as preterm birth, low birth weight and less optimal
scores on neonatal reflexes and behaviour. Pharmacological intervention is often
advised; however, this in itself has been associated with these outcomes, thus
creating a treatment dilemma. It is ethically and logistically impossible to carry out
long-term controlled studies into later effects of early life exposure to
antidepressants in a clinical population; animal models provide an alternative. The
present work aimed to investigate the developmental, behavioural and neurochemical
effects of exposure to the antidepressants amitriptyline and fluoxetine in the rat
following a variety of exposures: 1) prenatal exposure via maternal administration; 2)
prenatal and/or postnatal exposure via maternal administration and 3) direct postnatal
administration; direct administration of clomipramine was also investigated as
behavioural and neurochemical changes have been seen previously with this drug.
Administration of the drugs during gestation was not found to result in maternal
toxicity, as no decreases in body weight were observed. Birth weight was found to be
decreased following exposure to both drugs via maternal administration and there
were sporadic alterations in body weight throughout the neonatal period. Direct drug
administration decreased body weight during the dosing period, but these decreases
did not endure once drug administration ceased. All drugs had effects on anxiety-like
behaviour in the elevated plus maze; however these effects were dependent upon
duration of exposure and age of testing. There were no effects of drug exposure in
the forced swim test, a model of ¿behavioural despair¿ or on spatial learning and
memory in the Morris water maze. There were transient changes in monoamine
levels following prenatal exposure to amitriptyline and fluoxetine, but no effects of
direct administration of any drug were seen on this parameter or on the number of
tryptophan hydroxylase cells in the dorsal raphe nucleus. A number of sex effects
were seen, with females exhibiting a delay in acquisition of the surface righting
reflex, increased locomotor activity in the open field during adulthood and decreased
immobility in the forced swim test. This research has shown that early exposure to
the antidepressants amitriptyline and fluoxetine results in transient changes in body
weight, anxiety-like behaviour and monoamine levels. It is recommended that the
behavioural profile presented herein be expanded upon in order to better determine
the extent of behavioural teratogenicity of these drugs.