Prenatal immune activation potentiates endocannabinoid-related plasticity of inhibitory synapses in the hippocampus of adolescent rat offspring

Eur Neuropsychopharmacol. 2018 Dec;28(12):1405-1417. doi: 10.1016/j.euroneuro.2018.09.003. Epub 2018 Sep 23.


There is strong evidence that immune activation from prenatal infection increases the risk for offspring to develop schizophrenia. The endocannabinoid (eCB) system has been implicated in the pathophysiology of schizophrenia while models of cortical dysfunction postulate an imbalance between neuronal excitation and inhibition in the disorder. The current study examined the impact of prenatal immune activation on eCB-mediated inhibitory mechanisms. We compared two forms of eCB-related plasticity of evoked inhibitory postsynaptic currents, namely depolarization-induced suppression of inhibition (DSI) and metabotropic glutamate receptor-induced long term depression (mGluR-iLTD), in both the dorsal and ventral hippocampus between adolescent offspring from rat dams that received either saline or bacterial lipopolysaccharide (LPS) during pregnancy. Compared to prenatal saline offspring, prenatal LPS offspring displayed prolonged DSI and stronger mGluR-iLTD in the dorsal and ventral hippocampus, respectively. The sensitivity of mGluR-iLTD to the CB1 receptor antagonist AM251 was also lower in the dorsal hippocampus of prenatal LPS compared to prenatal saline offspring. Testing whether changes in eCB receptor signaling or levels could contribute to these changes in inhibitory transmission, we found region specific increases in 2-arachidonoylglycerol-stimulated signaling and in basal and mGluR-induced levels of anandamide in prenatal LPS offspring when compared to prenatal saline offspring. Our findings indicate that prenatal immune activation can lead to long-term changes in eCB-related plasticity of hippocampal inhibitory synaptic transmission in adolescent rat offspring. Perturbation of the eCB system resulting from prenatal immune activation could represent a mechanism linking early life immune events to the development of psychopathology in adolescence.

Keywords: Electrophysiology; Endocannabinoid; Hippocampus; Inhibition; Prenatal infection; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Endocannabinoids / metabolism*
  • Escherichia coli
  • Female
  • Hippocampus / growth & development*
  • Hippocampus / immunology*
  • Lipopolysaccharides
  • Male
  • Neural Inhibition / immunology*
  • Neuroimmunomodulation / physiology
  • Neuronal Plasticity / immunology*
  • Pregnancy
  • Pregnancy Complications, Infectious / immunology*
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / metabolism
  • Sexual Maturation
  • Synaptic Transmission / immunology
  • Tissue Culture Techniques


  • Cnr1 protein, rat
  • Endocannabinoids
  • Lipopolysaccharides
  • Receptor, Cannabinoid, CB1