Postretrieval Microinjection of Baclofen Into the Agranular Insular Cortex Inhibits Morphine-Induced CPP by Disrupting Reconsolidation

Abstract

Environmental cues associated with drug abuse are powerful mediators of drug craving and relapse in substance-abuse disorders. Consequently, attenuating the strength of cuedrug memories could reduce the number of factors that cause drug craving and relapse. Interestingly, impairing cue-drug memory reconsolidation is a generally accepted strategy aimed at reducing the intensity of cues that trigger drug-seeking and drug-taking behaviors. In addition, the agranular insular cortex (AI) is an important component of the neural circuits underlying drug-related memory reconsolidation. GABA B receptors (GABA B Rs) are potential targets for the treatment of addiction, and baclofen (BLF) is the only prototypical GABA B agonist available for application in clinical addiction treatment. Furthermore, DFosB is considered a biomarker for the evaluation of potential therapeutic interventions for addiction. Here, we used the morphine-induced conditioned place preference (CPP) paradigm to investigate whether postretrieval microinjections of BLF into the AI could affect reconsolidation of drug-reward memory, reinstatement of CPP, and the level of DFosB in mice. Our results showed that BLF infused into the AI immediately following morphine CPP memory retrieval, but not 6 h postretrieval or following nonretrieval, could eliminate the expression of a morphine CPP memory. This effect persisted in a morphine-priming-induced reinstatement test, suggesting that BLF in the AI was capable of preventing the reconsolidation of the morphine CPP memory. Our results also showed that the elimination of morphine CPP memory was associated with reduced morphine-associated DFosB expression in the longer term. Taken together, the results of our research provide evidence to support that GABA B Rs in the AI have an important role in drug-cue memory reconsolidation and further our understanding of the role of the AI in drug-related learning and memory.

Global Cerebral Ischemia in Male Long Evans Rats Impairs Dopaminergic/ΔFosB Signalling in the Mesocorticolimbic Pathway Without Altering Delay Discounting Rates

“…Negative controls (without primary antibody) ensured secondary antibody specificity and pilot studies determined optimal primary antibody concentrations. Staining and expression was similar to previous studies (See Larson and Ariano, 1995 for DRD 2 ; Sun et al, 2020 for ΔFosB; and Threlfell et al, 2021 for DAT). For DRD 2 , antigen retrieval was performed prior to blocking.…”

Continuous High Frequency Deep Brain Stimulation of the Rat Anterior Insula Attenuates the Relapse Post Withdrawal and Strengthens the Extinction of Morphine Seeking

“…Several studies have demonstrated that stroke-induced insula damage could lead to an abrupt and profound disruption of addiction to cigarette smoking without relapsing and craving ( 12 , 13 ), and patients in the insula lesion group quit heroin use entirely at a higher rate than controls ( 14 ). In addition, an array of recent studies using animal models and pharmacological or chemical interventions have showed that insula is involved in different aspects of addictive behavior of various addictive drugs ( 15 – 20 ). For example, morphine-induced conditioned place preference (CPP) in rats were attenuated in studies using administration of muscarinic acetylcholine receptor antagonists and nitric oxide inhibitors into insula ( 21 , 22 ).…”

Medial prefrontal cortex Notch1 signalling mediates methamphetamine-induced psychosis via Hes1-dependent suppression of GABAB1 receptor expression

“…DAPT or vehicle was administered via bilateral intracranial microinjections at 0.5 μL/hemisphere. The GABA B receptor agonist baclofen (Sigma, USA) and the GABA B receptor antagonist phaclofen (Sigma, USA) were dissolved in saline and administered at doses of 0.06 nmol/0.2 μL/mouse [ 32 ] and 0.1 nmol /0.2 μL/ mouse [ 33 ], respectively.…”