In vivo reduction of hippocampal Caveolin-1 by RNA interference alters morphine addiction and neuroplasticity changes in male mice. (1st April 2021)

• Record Type: Journal Article
• Authors: Wang, Shanshan; Zeng, Min; Ren, Yi; Han, Song; Li, Junfa; Cui, Weihua
• Is Part Of: Neuroscience letters. Volume 749(2021)
• Publication Date: 2021-04-01
• Subjects: NAc nucleus accumbens -- mPFC medial prefrontal cortex -- VTA ventral tegmental area -- HPC hippocampus -- MOR μ-opioid receptor -- Cav-1 caveolin-1 -- MLRs membrane lipid rafts -- GPCRs G protein-coupled receptors -- MAP-2 microtubule-associated protein 2 -- CPP conditioned place preference; Morphine -- Cav-1 -- Membrane lipid rafts -- Neuronal plasticity -- Rewarding effects; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2021.135742
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: This study revealed an essential role of hippocampal Cav-1 in the neuroplasticity changes that underlie morphine addiction behaviors. Knockdown of Cav-1 in the hippocampus inhibited chronic morphine-induced conditioned place preference but not locomotor hyperactivity. Knockdown of Cav-1 decreased chronic morphine-induced dendritic growth in the hippocampus. Abstract: Prescription opioids are powerful pain-controlling medications that have both benefits and potentially serious risks. Morphine is one of the preferred analgesics that are widely used to treat chronic pain. However, chronic morphine exposure has been found to cause both functional and structural changes in several brain regions, including the medial prefrontal cortex (mPFC), ventral tegmental area (VTA), and hippocampus (HPC), which lead to addictive behavior. Caveolin-1 (Cav-1), a scaffolding protein of membrane lipid rafts (MLRs), has been shown to organize GPCRs and multiple synaptic signaling proteins within the MLRs to regulate synaptic signaling and neuroplasticity. Previously, we showed that in vitro morphine treatment significantly elevates Cav-1 expression and causes neuroplasticity changes. In this study, we confirmed that chronic morphine exposure can significantly increase Cav-1 expression (P < 0.05) and microtubule-associated protein (MAP-2)-positive neuronal dendritic growth in the hippocampus. Moreover, the rewarding effect and dendritic growth in the HPC induced by chronic morphine exposure were significantly inhibited by hippocampal Cav-1 knockdown. Together, these data suggest that Cav-1 in the hippocampus plays an essential role in the neuroplasticity changes that underlie morphine addiction behaviors.