Minocycline Attenuates Lipopolysaccharide-Induced Locomotor Deficit and Anxiety-like Behavior and Related Expression of the BDNF/CREB Protein in the Rat Medial Prefrontal Cortex (mPFC)

Int J Mol Sci. 2022 Nov 3;23(21):13474. doi: 10.3390/ijms232113474.

Abstract

Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficits and anxiety-like behaviour. In this study, minocycline was compared to memantine, an NMDA receptor antagonist, for its effects on LPS-induced locomotor deficits and anxiety-like behaviour in rats. Adult male Sprague Dawley rats were administered either two different doses of minocycline (25 or 50 mg/kg/day, i.p.) or 10 mg/kg/day of memantine (i.p.) for 14 days four days prior to an LPS (5 mg/kg, i.p.) injection. Locomotor activity and anxiety-like behaviour were assessed using the open-field test (OFT). The phosphorylated tau protein level was measured using ELISA, while the expression and density of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and Western blot, respectively. Minocycline treatment reduced locomotor deficits and anxiety-like behaviour associated with reduced phosphorylated tau protein levels, but it upregulated BDNF/CREB protein expressions in the mPFC in a comparable manner to memantine, with a higher dose of minocycline having better benefits. Minocycline treatment attenuated LPS-induced locomotor deficits and anxiety-like behaviour in rats and decreased phosphorylated tau protein levels, but it increased the expressions of the BDNF/CREB proteins in the mPFC.

Keywords: anxiety-like behaviour; lipopolysaccharide; locomotor deficit; medial prefrontal cortex; memantine; minocycline.

MeSH terms

  • Animals
  • Anxiety / drug therapy
  • Anxiety / metabolism
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Cyclic AMP Response Element-Binding Protein* / metabolism
  • Gait Disorders, Neurologic
  • Lipopolysaccharides / pharmacology
  • Male
  • Memantine / pharmacology
  • Minocycline / pharmacology
  • Prefrontal Cortex / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • tau Proteins / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Lipopolysaccharides
  • Memantine
  • Minocycline
  • tau Proteins