Clonidine, an α2 adrenergic receptor agonist, disrupts reconsolidation of a cocaine-paired environmental memory

Abstract

Environmental cues can elicit robust cocaine reward memories, contributing to relapse to cocaine abuse. Memories can be manipulated pharmacologically by interfering with reconsolidation after reactivation. Clonidine, an α2 noradrenergic receptor agonist, was tested for its ability to block reconsolidation of cocaine environmental-paired memory. Male Sprague-Dawley rats completed an 8-day cocaine place conditioning procedure to establish a cocaine place preference. Cocaine memory was reactivated by exposure to the cocaine-paired environment in a drug-free state, followed immediately by administration of clonidine (10 or 50 µg/kg) or vehicle. Cocaine place preference was retested 24 h and 1 week later. Clonidine significantly attenuated the previously established cocaine place preference when tested 1 or 7 days later. To investigate the generalizability of this effect to other drug classes, morphine conditioned place preference was tested. Clonidine administration after morphine memory reactivation did not significantly alter the expression of morphine place preference. These results suggest that clonidine can interfere with reconsolidation of cocaine memory and may be a useful approach to reduce relapse.

The Ameliorative Effects of Isorhynchophylline on Morphine Dependence Are Mediated Through the Microbiota-Gut-Brain Axis

“…The results indicated that concomitant administration of multiple antibiotics changed the composition and proportion of the species that comprise the intestinal flora. Pathway-enrichment analysis showed that morphine treatment upregulated five pathways and decreased seven metabolic pathways, eight of which (Cardiovascular disease, Endocrine System, Circulatory System, Cellular Processing and Signaling, Energy metabolism, Genetic Information Processing, Immune System disease, and Environmental Adaption) are closely associated with morphine use ( Tung et al, 2015 ; Gimenez-Mila et al, 2016 ; Balyan et al, 2017 ; Hakimian et al, 2017 ; Park et al, 2017 ; de Vries et al, 2019 ; Denny and Unterwald, 2019 ; Mutua et al, 2019 ). In accordance with the results for GM composition, no differences were observed in the regulation of the above metabolic pathways in the GM of A-, A + M-, A + M + M-, and A + M + I-treated zebrafish after antibiotic treatment.…”

Drug memory reconsolidation: from molecular mechanisms to the clinical context

“…Another catecholamine, noradrenaline, is also required for drug memory reconsolidation. Agonising α 2 receptors with clonidine disrupts cocaine CPP [ 105 ], and antagonising β-adrenergic receptors with systemic propranolol during a single CPP memory reactivation session impairs subsequent CPP for cocaine [ 106 ], morphine [ 107 ] and nicotine [ 108 ], although not alcohol [ 109 ]. However, propranolol appears less effective when the drug CPP memory is strong, particularly if the memory has been recently acquired [ 110 ].…”

Hippocampus-sensitive and striatum-sensitive learning one month after morphine or cocaine exposure in male rats

“…On each of five consecutive days, rats received an injection (i.p., 1 ml / kg) of either 0.9% saline, cocaine (20 mg / kg; Sigma-Aldrich, St. Louis, MO), or morphine (5 mg / kg; Sigma). Drug doses were chosen to match those shown to support conditioned place preference (Denny and Unterwald, 2019;White et al, 2005). Cocaine and morphine exposure induced modest weight loss during the five-day injection period while the saline rats increased their weight at that time (weight changes: saline, +4.3 ± 0.8 gm; cocaine: -3.3 ± 1.5 gm; morphine: -1.9 ± 1.1 gm).…”