Adolescent morphine induces emotional signs of withdrawal paired with neurotoxicity selectively in male rats: Female resilience
Neuroscience Letters. 2020-01-01; 715: 134625
DOI: 10.1016/j.neulet.2019.134625
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Jiménez-Romero F(1), Bis-Humbert C(1), García-Fuster MJ(2).
Author information:
(1)IUNICS, University of the Balearic Islands, Palma, Spain; IdISBa, Palma,
Spain.
(2)IUNICS, University of the Balearic Islands, Palma, Spain; IdISBa, Palma,
Spain. Electronic address: .
This study evaluated the immediate and persistent behavioral and molecular
consequences (i.e., emotional signs emerging during withdrawal and signs of
neurotoxicity) following adolescent morphine exposure with a sex perspective.
Basally, and prior to drug treatment, adolescent female rats showed smaller body
weight and lower pain threshold than their male counterparts. Adolescent
morphine treatment induced some sex-specific differences, while morphine
impaired normal weight gain in male rats, no effects were observed for female
rats. Plus, morphine produced an attenuated antinociceptive response in female
rats. Moreover, following adolescent morphine treatment some emotional signs of
withdrawal emerged exclusively in male rats in conjunction with signs of
neurotoxicity, while female rats were not affected. In particular, an
anxiolytic-like effect in adolescence during early withdrawal was followed by
the development of a depressive-like phenotype (i.e., behavioral despair,
anxiety-like behavior and anhedonia) in adulthood during prolonged withdrawal
and paired with decreased contents of neurofilaments proteins in the prefrontal
cortex. In conclusion, morphine administration during adolescence induced
persistent changes in negative affect and brain toxicity selectively in male
rats, suggesting female rats were resilient to these harmful effects. Given the
widespread availability and use of opiate-based painkillers, the interplay
between addiction, analgesia and emotional behaviors, and since adolescents and
young adult humans are the age group with the highest abuse potential, these
results add to the current literature by reporting distinct sex-specific opioid
actions when administered in adolescence.
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