[Abstract Title]. - Society for Neuroscience

Poster
255. Mood Disorders: Animal Models and Treatment Effects II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 255.19/Y34
Topic: C.15.h. Affective disorders: Animal models
Support: NIDA-NIH 1R21 DA024099-01
Title: The antibiotic minocycline increases phosphorylation and membrane insertion of the
neuronal GluR1 glutamate/AMPA receptor subunit
Authors: *M. IMBESI, T. UZ, N. DIMITRIJEVIC, R. MANEV, R. SHARMA, H. MANEV;
Psychiatry, UIC, Chicago, IL
Abstract: Increased phosphorylation of the glutamate receptor subunit GluR1 at Ser845 and
Ser831 is associated with the increased membrane insertion of this AMPA-sensitive receptor.
GluR1 phosphorylation plays a role in the antidepressant action of various antidepressants
(phosphorylation is increased) and in the addictive components of cocaine. Recently, we
demonstrated that 5-lipoxygenase (5-LOX) inhibitors increase GluR1 phosphorylation, that they
may have antidepressant activity, and also may influence the behavioral effects of cocaine.
Minocycline is a neuroprotective tetracycline antibiotic that also inhibits 5-LOX (Brain Res
2006, 1085:57-67) and exerts antidepressant-like activity (Prog Neuropsychopharmacol Biol
Psychiatry 2008, 32:380-6). We hypothesized that minocycline may share similarities with 5-
LOX inhibitors with respect to GluR1 and behavior. In this study, we investigated the effects of
minocycline on GluR1 phosphorylation and membrane insertion in primary cultures of mouse
striatal neurons and in the prefrontal cortex of adult male mice treated with intraperitoneal
minocycline injections. GluR1 phosphorylation was measured using GluR1 phospho-Ser845 and
phospho-Ser831 antibodies (Brain Res 2007, 1147:148-53) and GluR1 membrane insertion was
measured using the BS3 assay (J Neurosci 2007, 27:10621-35). In-vitro, low micromolar
concentrations of minocycline increased GluR1 phosphorylation at Ser845 and Ser831 and
increased the membrane content of GluR1. Also, in-vivo minocycline treatment increased GluR1
phosphorylation. In a forced swim test, minocycline increased climbing behavior and decreased
immobility; i.e., produced antidepressant-like behavior (Prog Neuropsychopharmacol Biol
Psychiatry 2008). Interestingly, a single case report described the antidepressant effects of
minocycline in humans (Am J Psychiatry, 1996, 153:582), suggesting that our findings might
have clinical implications. Further studies should investigate whether the effects of minocycline
on GluR1 are involved in the behavioral activity of this antibiotic (e.g., antidepressant and
modification of cocaine's behavioral effects), and whether the effects of minocycline involve 5-
LOX inhibition.
Disclosures: M. Imbesi , None; T. Uz, None; N. Dimitrijevic, None; R. Manev, None; R.
Sharma, None; H. Manev, None.