Morphine Treatment in Neonate Rats Increases Exploratory Activities: Reversal by Antagonist D2 Receptor.
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Date
2014-01-01
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Abstract
Aims: Morphine treatment in early life is a practice widely used in paediatric intensive
care units. However, the consequences of this treatment on behavioural responses
throughout life have been poorly studied. It is well known that behavioural symptoms after
morphine exposure are presumed to depend on certain changes in the dopaminergic
system, and there is a strong evidence of the involvement of D2 receptor. In this way, our
objective was to evaluate whether 5 μg morphine administration, once daily for 7 days in
8-day-old rats (P8), alters exploratory and anxiolitic-like behaviours over short- (P16) and medium-term (P30) periods in the open-field (OF) and elevated-plus maze (EPM) tests,
and to verify the involvement of the D2 receptor in the behaviour changes.
Place of Study: All experiments were performed at Animal Experimentation Unit of
Hospital de Clínicas de Porto Alegre. The experimental protocol was approved by the
Institutional Committee for Animal Care and Use (GPPG-HCPA protocol No: 08345).
Methodology: Wistar rats with 8-day-old (P8) received 5 μg of morphine administration,
once daily for 7 days. The exploratory and anxiolitic-like behavious were analyzed in P16
and P30 by OF and EPM tests. At the ages where we observed significant differences in
behaviour responses in both tests, the control and morphine groups were subdivided into
three groups, each one designed to evaluate the effect of 0.2 mg/kg, 0.5 mg/kg or vehicle
of i.p. administration of a dopamine D2 antagonist receptor (Haloperidol).
Results: At short-term (P16) morphine group showed an increase in grooming, as well
increase in exploratory behaviours at P30 in the OF test. In addition, anxiolytic-like
behaviours were observed in the morphine group, such as increase of percentage of
open arms behaviours and non-protected head dipping at medium-term in the EPM test.
At the ages at which differences in behaviours were observed, both groups (control and
morphine) received D2 antagonist receptor (haloperidol) 30 min before each test. All
behaviours changes seen in the morphine group at P30 were totally reversed by
haloperidol administration.
Conclusion: Our findings demonstrate that morphine treatment in neonate period
promotes behavioural changes in OF and EPM at P16 and P30. However, only
alterations observed at P30 depend, at least in part, of dopaminergic system, particularly
of the D2 receptor.
Description
Keywords
Morphine, open-field test, elevated-plus-maze test, exploratory-like behaviour, D2 receptor, neonate rat
Citation
Rozisky Joanna R, Laste Gabriela, Medeiros Liciane F, Santos Vinicius S Dos, Adachi Lauren S, Macedo Isabel C De, Caumo Wolnei, Torres Lraci L S. Morphine Treatment in Neonate Rats Increases Exploratory Activities: Reversal by Antagonist D2 Receptor. British Journal of Medicine and Medical Research. 2014 Jan; 4(1): 351-367.