Chronic treatment with fluoxetine induces sex-dependent analgesic effects and modulates HDAC2 and mGlu2 expression in female mice
Front. Pharmacol.. 2017-10-20; 8:
DOI: 10.3389/fphar.2017.00743
Read on PubMed
Zammataro M(1), Merlo S(2), Barresi M(3), Parenti C(1), Hu H(4), Sortino MA(2), Chiechio S(1).
Author information:
(1)Department of Drug Sciences, University of Catania, Catania, Italy.
(2)Department of Biomedical and Biotechnological Sciences, University of Catania,
Catania, Italy.
(3)Institut des Maladie Neurodégénératives, Bordeaux, France.
(4)Department of Pharmacology and Physiology, Drexel University College of
Medicine, Philadelphia, PA, United States.
Gender and sex differences in pain recognition and drug responses have been
reported in clinical trials and experimental models of pain. Among
antidepressants, contradictory results have been observed in patients treated
with selective serotonin reuptake inhibitors (SSRIs). This study evaluated sex
differences in response to the SSRI fluoxetine after chronic administration in
the mouse formalin test. Adult male and female CD1 mice were intraperitoneally
injected with fluoxetine (10 mg/kg) for 21 days and subjected to pain assessment.
Fluoxetine treatment reduced the second phase of the formalin test only in female
mice without producing behavioral changes in males. We also observed that
fluoxetine was able to specifically increase the expression of metabotropic
glutamate receptor type-2 (mGlu2) in females. Also a reduced expression of the
epigenetic modifying enzyme, histone deacetylase 2 (HDAC2), in dorsal root
ganglia (DRG) and dorsal horn (DH) together with an increase histone 3
acetylation (H3) level was observed in females but not in males. With this study
we provide evidence that fluoxetine induces sex specific changes in HDAC2 and
mGlu2 expression in the DH of the spinal cord and in DRGs and suggests a
molecular explanation for the analgesic effects in female mice.
DOI: 10.3389/fphar.2017.00743
PMCID: PMC5654865
PMID: 29104538