Neurotensin and Alcohol Use Disorders: Towards a Pharmacological Treatment

Abstract

Harmful alcohol use is responsible for a group of disorders collectively named alcohol use disorders (AUDs), according to the DSM-5 classification. The damage induced by alcohol depends on the amount, time, and consumption patterns (continuous and heavy episodic drinking). It affects individual global well-being and social and familial environments with variable impact. Alcohol addiction manifests with different degrees of organ and mental health detriment for the individual, exhibiting two main traits: compulsive drinking and negative emotional states occurring at withdrawal, frequently causing relapse episodes. Numerous individual and living conditions, including the concomitant use of other psychoactive substances, lie in the complexity of AUD. Ethanol and its metabolites directly impact the tissues and may cause local damage or alter the homeostasis of brain neurotransmission, immunity scaffolding, or cell repair biochemical pathways. Brain modulator and neurotransmitter-assembled neurocircuitries govern reward, reinforcement, social interaction, and consumption of alcohol behaviors in an intertwined manner. Experimental evidence supports the participation of neurotensin (NT) in preclinical models of alcohol addiction. For example, NT neurons in the central nucleus of the amygdala projecting to the parabrachial nucleus strengthen alcohol consumption and preference. In addition, the levels of NT in the frontal cortex were found to be lower in rats bred to prefer alcohol to water in a free alcohol–water choice compared to wild-type animals. NT receptors 1 and 2 seem to be involved in alcohol consumption and alcohol effects in several models of knockout mice. This review aims to present an updated picture of the role of NT systems in alcohol addiction and the possible use of nonpeptide ligands modulating the activity of the NT system, applied to experimental animal models of harmful drinking behavior mimicking alcohol addiction leading to health ruin in humans.

The Therapeutic Role of Olea europaea in Alcohol Dependence Base in Network Pharmacology Analysis

“…These receptors are involved in the attribution of important meanings of incentives to sensory signals, learning avoidance, motivation, influence regulation, and decision-making (Weiland et al, 2020). CNR1 can enhance endocannabinoid functions and restore affective homeostasis without alcohol, thereby reducing or eliminating the incentive to consume alcohol because of its negative strengthening properties (Rodr et al, 2023). ARRB2 (β-arrestin2), which influences the function of dopamine two receptors (D2R) as an intracellular signal and release of Gamma-Aminobutyric Acid (GABA) (Lyoo et al, 2014).…”

Orphan peptide and G protein‐coupled receptor signalling in alcohol use disorder

“…Of these, 73 assess drug interventions and 44 (60%) target GPCR mechanisms including 5‐HT receptors (14/44, 31%), cannabinoid receptors (8/44, 18%), oxytocin receptors (6/44, 13%), and GLP1 receptor (4/44, 9%) (see Table 1 for summary). A variety of other GPCR targets for AUD are in preclinical development including, but not limited to, muscarinic receptors (Walker et al, 2020 , 2023 ), neurotensin receptors (Rodriguez et al, 2023 ), and neurokinin receptors (Schank, 2020 ). These data highlight the potential of GPCR signalling to treat AUD, a topic that is being widely explored.…”