0000000000321764
AUTHOR
Marco Diana
Naltrexone antagonizes acetaldehyde-induced increments in dopamine neurons activity
Abstract Acetaldehyde is the main metabolite of ethanol ingested through alcoholic beverages. Traditionally considered aversive is presently being viewed as an activating agent of the mesolimbic dopamine system but underlying mechanisms are only partially known. Here we show that acetaldehyde-induced increase in firing rate, burst firing and spikes/burst of antidromically-identified ventro-tegmental area Nucleus Accumbens-projecting neurons are abolished by pretreatment with the opiate unselective antagonist naltrexone (1mg/kg/ip). Similar effects are obtained after administration of naloxone (0.1mg/kg/iv). These results indicate: 1) endogenous opiate system(s) participate in acetaldehyde-i…
Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats.
Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95…
Bilateral Transcranial Magnetic Stimulation of the Prefrontal Cortex Reduces Cocaine Intake: A Pilot Study
Background Chronic cocaine consumption is associated with a decrease in mesolimbic dopamine transmission that maintains drug intake. transcranial magnetic stimulation (TMS) is gaining reliability, a useful therapeutic tool in drug addiction, since it can modulate cortico-limbic activity resulting in reduction of drug craving. Aims In the present study, we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). Methods Ten cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve …
Activity of orally self-administered acetaldehyde in an operant/conflict paradigm in rats; involvement of cannabinoid cb1 receptors
Acetaldehyde (ACD), ethanol first metabolite, interacts with the dopaminergic reward system, and with the neuropeptidergic transmission in the hypothalamus. Self-administration within operant conditioning is a valid model to investigate drug-seeking and drug-taking behaviour in rats. Cannabinoid CB1 receptors are involved in reinstatement of alcohol-seeking behaviour and of many other drugs of abuse (3). Accordingly, this study was aimed at the evaluation of: 1) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behaviour; 2) the onset of a relapse drinking behaviour, following ACD deprivation; 3) ACD effect in a conflict situation employing the …
Dopamine restores limbic memory loss, dendritic spine structure, and NMDAR-dependent LTD in the nucleus accumbens of alcohol-withdrawn rats
Alcohol abuse leads to aberrant forms of emotionally salient memory, i.e., limbic memory, that promote escalated alcohol consumption and relapse. Accordingly, activity-dependent structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing chronic alcohol consumption. Here we show that alcohol-dependent male rats fail to perform an emotional-learning task during abstinence but recover their functioning byl-3,4-dihydroxyphenylalanin (l-DOPA) administration during early withdrawal.l-DOPA also reverses the selective loss of dendritic “long thin” spines observed in medium spiny neurons of the nucleus accumbens (NAc) shell of alcohol-dependent rats d…
Transcranial Electrical and Magnetic Stimulation (tES and TMS) for Addiction Medicine: A Consensus Paper on the Present State of the Science and the Road Ahead
International audience; There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic…
Cannabis and the Mesolimbic System
Abstract Cannabis sativa (hemp) is a flowering annual plant whose phytochemical by-products, hashish and marihuana, are the most widely produced and most frequently used illicit drugs in Europe. Δ 9 -Tetrahydrocannabinol is the primary psychoactive constituent, responsible, in a dose-related manner, for euphoria, cognitive effects, and psychotic symptoms, as well as the addictive potential of smoked cannabis due to its interference with the mesolimbic dopaminergic system. Cannabis as well as endocannabinoids acts mainly at the presynaptic levels in several brain regions, including the nucleus accumbens and ventral tegmental area, where it modulates synaptic activity. Through the modulation …