title: Phosphodiesterase 4 inhibitors enhance sexual pleasure-seeking activity in rodents.
abstract: Pleasure-seeking deficits, including lack of libido, are a core feature of depression. Animal and preliminary clinical studies both suggest that phosphodiesterase 4 (PDE4) is a target for developing novel antidepressants. This study examined the potential involvement of PDE4 in the pathology of depression in both animal models and human postmortem brains. In humans, PDE4B and PDE4D levels were elevated in cingulate cortical tissue from individuals with major depressive disorder (MDD) compared to controls. Using the female urine smelling test (FUST), a recently refined method for monitoring sexual pleasure-seeking activity in mice, we found that icv infusion of selective potent PDE4 inhibitors enhanced sexual pleasure-seeking activity in male mice that underwent the learned helplessness or serotonin depletion paradigms. The infusion also increased sexual pleasure-seeking activity in naïve male mice. The results suggest that PDE4 may be a plausible contributor to the sexual pleasure-seeking deficits seen in depressed patients; inhibiting PDE4 may restore these deficits.
authors.affiliation: Biomarker Laboratory, National Institute of Mental Health, Mood and Anxiety Disorders Program, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Peixiong
authors.initials: P
authors.lastname: Yuan
authors.forename: Tyson
authors.initials: T
authors.lastname: Tragon
authors.forename: Menghang
authors.initials: M
authors.lastname: Xia
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Leclair
authors.forename: Amanda P
authors.initials: AP
authors.lastname: Skoumbourdis
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Thomas
authors.forename: Ruili
authors.initials: R
authors.lastname: Huang
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Austin
authors.forename: Guang
authors.initials: G
authors.lastname: Chen
authors.forename: Xavier
authors.initials: X
authors.lastname: Guitart
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D008297:Male; D051379:Mice; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
chemical_list: D058988:Phosphodiesterase 4 Inhibitors