Alcohol and the brain: from genes to circuits PMC

Another type of MRI application, magnetic resonance spectroscopy imaging (MRSI), provides information about the neurochemistry of the living brain. MRSI can evaluate neuronal health and degeneration and can detect the presence and distribution of alcohol, certain metabolites, and neurotransmitters. However, it is not known whether this comparison between men and women holds among older populations (Oscar-Berman 2000).

Alcohol Overdose

These projections have been targeted to exert bidirectional, long-lasting control of alcohol drinking [103]. Furthermore, dysregulation of striatal function can produce pathological drinking behaviors. For instance, manipulations of striatal dopamine D2 receptors (D2Rs), adenosine 2A receptors, or activity of fast-spiking interneurons, among others, alter excessive drinking https://sober-home.org/5-key-differences-between-crack-and-cocaine/ behaviors [104–106]. Further, disrupted GABAergic transmission in this region is also linked to alcohol-induced cognitive impairments [107]. Together, altered excitability of striatal neurons and upstream cortical regulation of striatal activity influence a diverse range of drinking behaviors, which likely can be attributed to distinct striatal output circuits [108].

Beliefs vs. Reality: How to Weaken Your Alcohol Craving

Reverse translation of these findings into a rodent model demonstrated putative therapeutic potential for a positive allosteric modulator of the muscarinic M4 receptor which, when delivered systemically in rats, reduced a wide range of alcohol self-administration behaviors [70]. Additionally, receptor tyrosine kinases (RTKs) which are activated by growth factors and cytokines play a role in alcohol consumption [60]. For example, alcohol-dependent activation of the anaplastic lymphoma kinase (Alk) in the hippocampus and PFC activates STAT signaling leading to changes in gene expression, and systemic administration of Alk or Stat3 inhibitors attenuates alcohol intake in mice [61,62]. Surprisingly, a number of growth factors/RTKs such as Bdnf and the glial-derived neurotrophic factor (Gdnf) are endogenous factors that limit alcohol use [60,63].

How much can people drink safely?

The mechanisms that drive alcohol-dependent transcriptional alterations are still being unraveled (Figure 1). For example, the transcriptional activity of NF-κB is controlled through the stimulation of the inhibitor κβ kinase (IKKβ). Using pharmacologic and genetic approaches, Ikkβ was shown to contribute to excessive alcohol intake in mice [29], and its action is localized to neurons at least in the NAc and CeA [29]. Another example is the transcriptional regulator, LIM Domain Only 4 (Lmo4), which was shown to drive vast changes in gene expression in the basolateral amygdala (BLA) of mice in response to repeated exposure to alcohol and to the regulation of alcohol intake [30]. In addition to contributing to the mechanisms that drive excessive drinking (GO signaling), transcription factors are likely to contribute to the gating of alcohol intake (STOP signaling).

1. A study conducted by Harvard University found that social media has a significantly detrimental effect on the emotional well-being of chronic users and their lives, negatively impacting their real-life relationships and academic achievement.
2. Recognition of which of these processes are spared and which are impaired in a given patient could provide an empirical basis for targeted behavioral therapy during periods of recovery.
3. Repeated in vivo ethanol downregulates Ih density in dopamine neurons (Okamoto et al., 2006) and induces adaptations in the dopamine D2 receptor and GIRK channels (Perra et al., 2011) (Figure 3C).
4. Indeed, in the globus pallidus external segment, acute ethanol decreases the firing of low-frequency, but not high-frequency, firing neurons.

Another brain structure that has recently been implicated is the cerebellum (Sullivan 2000), situated at the base of the brain, which plays a role in posture and motor coordination and in learning simple tasks. The outer, convoluted layer of brain tissue, called the cerebral cortex or the gray matter, controls most complex mental activities (see figure 1). Just beneath it are the nerve fibers, called the white matter, that connect different cortical regions and link cortical cells with other structures deep inside the brain (subcortical regions). The largest DTI study of MBD to date included six study participants, five with a history of chronic alcoholism.

Ethanol Effects on Intrinsic Excitability, Synaptic Transmission, and Plasticity

During acute and protracted withdrawal, a profound negative emotional state evolves, termed hyperkatifeia (hyper-kuh-TEE-fee-uh). Only recently have radiotracers specific for characterizing excitatory glutamate receptors been developed. Early findings indicate impaired mGluR5 signaling to be involved in compulsive alcohol consumption [151]. These effects are found to be reversible following 28 days of abstinence and so can be viewed as a target to aid withdrawal [152].

In the absence of a cure for alcoholism, a detailed understanding of the actions of alcohol on nerve cells may help in designing effective therapies. Brain cells (i.e., neurons) communicate using specific chemicals called neurotransmitters. Specialized synaptic receptors on the surface of neurons are sensitive to specific neurotransmitters. Alcohol can change the activity of neurotransmitters and cause neurons to respond (excitation) or to interfere with responding (inhibition) (Weiss and Porrino 2002), and different amounts of alcohol can affect the functioning of different neurotransmitters. Over periods of days and weeks, receptors adjust to chemical and environmental circumstances, such as the changes that occur with chronic alcohol consumption, and imbalances in the action of neurotransmitters can result in seizures, sedation, depression, agitation, and other mood and behavior disorders. Studies of people who have alcohol-related cirrhosis with HE have reported elevated MD in several white-matter bundles, including the corpus callosum, internal capsule, and frontal white matter (Kale et al. 2006), and effects on both FA and MD of occipital white matter (Kumar et al. 2008).

Ethanol drinking alters the NMDAR subtypes by insertion of the NR2C subunit at mPFC and insula synapses onto MSNs in the NAc core, but it leaves these receptors unchanged at glutamatergic inputs from amygdala (Seif et al., 2013). The mPFC and insula synapses appear to drive drinking in the face of aversive consequences, and the NR2C subunit is implicated in the loss of this control (Seif et al., 2013). In addition, projections from the ventral subiculum to the NAc shell are also important for ethanol seeking in the face of aversive consequences, as selective inhibition of this pathway by chemogenetic techniques decreased context-induced relapse (Marchant et al., 2016).

The ongoing exposure to unrealistic beauty standards through social networking sites can affect how teenagers perceive their own bodies. One study from the University of Pittsburgh found a correlation between time spent scrolling through social media apps and negative body image feedback. Those who had spent more time on social media had 2.2 times the risk of reporting eating and body image concerns when compared to their peers who spent less time on social media.

The expansion of the fluid-filled spaces of the brain was interpreted as a sign of local tissue shrinkage rather than as irreversible tissue loss (i.e., atrophy) (Ron et al. 1982). Early neuropsychological studies of alcoholism often focused on KS and used test batteries (e.g., the Wechsler-Bellevue, Halstead-Reitan, Luria-Nebraska tests) that were quantitative and standardized but not necessarily selective to specific components of cognitive functions. Nonetheless, difficulties in performing tests of visuospatial ability were commonly identified with the Wechsler tests of intelligence (Victor https://sober-home.org/ et al. 1989). A striking feature of alcoholics is their continued drinking despite their knowledge of the untoward physiological or psychological consequences of their behavior. This characteristic became one of the diagnostic criteria for alcohol dependence specified in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM–IV) (American Psychiatric Association 1994). It also fits the description of people with lesions of the frontal lobes, who are characterized as “impulsive, inconsiderate, uninhibited, inflexible, or ill-mannered….” (Brewer 1974, p. 41).

This article focuses on MRI, DTI, and MRS findings in neurological disorders that commonly co-occur with alcoholism, including Wernicke’s encephalopathy, Korsakoff’s syndrome, and hepatic encephalopathy. Also reviewed are neuroimaging findings in animal models of alcoholism and related neurological disorders. This report also suggests that the dynamic course of alcoholism presents a unique opportunity to examine brain structural and functional repair and recovery.

The researchers said that switching our attention between social media, smartphones, tablets as well as TV, radio, or other media “harms our ability to complete simple tasks”. A 2022 survey by the Policy Institute and Centre for Attention Studies at King’s College London (KCL) found that 49% of people feel their attention span is shorter than it used to be. It also revealed that UK adults underestimate how often they check their phones by a great deal, thinking they check their devices 25 times a day on average when the reality suggests they check them closer to 80 times a day. “Brain rot” is a relatively new term coined on social media to describe the impact of being online nearly constantly. While it’s not a medical term, it has been used widely by platforms like TikTok and is the subject of numerous memes and videos. Ethanol can also interact directly with non-ion-channel targets, including intracellular signaling molecules such as protein kinase C (PKC) (Pany and Das, 2015; Ron and Barak, 2016) and adenylate cyclase (AC) (Yoshimura et al., 2006).

Behavioral neuroscientists have determined that the anterior region of the frontal lobes (i.e., the prefrontal cortex) is important for engaging in ordinary cognitive, emotional, and interpersonal activities. Disruptions of the normal inhibitory functions of prefrontal networks often have the interesting effect of releasing previously inhibited behaviors. As a result, a person may behave impulsively and inappropriately, which may contribute to excessive drinking.

These studies initiated exploration of ethanol’s actions on ion channels, which has become central to the neurobiology of alcohol. One prescient study by Davidoff (1973) found that ethanol enhanced neurotransmission using the neurotransmitter γ-aminobutyric acid (GABA) in the spinal cord. This was ignored until the mid-1980s (e.g., Allan and Harris 1986), but since then, GABA receptors have emerged as a major target of ethanol’s actions and continue to be an area of intense research interest (Kumar et al. 2009).

Mice that have been exposed to chronically elevated levels of alcohol reveal increased numbers of NMDA receptors and NMDA related seizure activity. The NMDA antagonist MK801 has been shown to decrease the severity of seizures in these mice during withdrawal. Through a complex process of cell membrane ion pumps and neurotransmitter stimulation, the multi-faceted effects of alcohol and alcohol withdrawal are becoming better understood.

These results suggest that the adolescent rodent brain may be more vulnerable to enduring toxic effects of EtOH than the adult rodent brain. Short-term (6 weeks) abstinence seems sufficient to observe some brain-volume recovery but does not result in equivalent brain volumes between recovering chronic alcoholics and healthy controls (Mann et al. 2005). That is, older alcoholics exhibit reduced capacity for recovery compared with younger alcoholics (Fein et al. 1990; Munro et al. 2000; Reed et al. 1992; Rourke and Grant 1999).

Together, medication and behavioral health treatments can facilitate functional brain recovery. In short, alcohol use during adolescence can interfere with structural and functional brain development and increase the risk for AUD not only during adolescence but also into adulthood. To help clinicians prevent alcohol-related harm in adolescents, NIAAA developed a clinician’s guide that provides a quick and effective screening tool (see Resources below). In summary, alcohol can contribute to neurotoxicity via thiamine deficiency, metabolite toxicity and neuroinflammation. Alcohol reduces the uptake and metabolism of thiamine, the essential co-factor without which glucose breakdown and the production of essential molecules cannot occur. This leads to neurotoxicity and can lead to the development of conditions of WE and KP.

Another ion channel with notable ethanol sensitivity is the G-protein-coupled inwardly rectifying K+ channel (GIRK). Ethanol enhances GIRK channel function (Bodhinathan and Slesinger, 2013; Glaaser and Slesinger, 2017), and genetic studies have identified a 43-amino-acid C-terminal region that is crucial for this action of ethanol (Lewohl et al., 1999). Mice carrying a missense mutation in the GIRK channel showed a loss of ethanol-induced analgesia (Kobayashi et al., 1999), and GIRK3 subunit knockout mice showed ethanol conditioned place preference, which was absent in controls (Tipps et al., 2016). Using a crystal structure of a mouse inward rectifier containing a bound ethanol molecule and structure-based mutagenesis, investigators probed a putative hydrophobic ethanol-binding pocket in the cytoplasmic domains of GIRK channels (Aryal et al., 2009). Even though using low doses of radioactive substances that decay quickly minimizes the risks of radiation exposure, newer and safer methods have emerged, such as MRI methods. MRI is noninvasive, involves no radioactive risks, and provides both anatomical and functional information with high precision.

This type of abuse, along with other forms of cyberbullying, has led to increased suicide rates among young adults. Additionally, these factors have also contributed to the development of increased levels of anxiety in teens and adolescents. Recent studies have found that frequent social network users believe that other users are happier and more successful than they are, especially when they do not know them very well in real life. Social media facilitates an environment in which people are comparing their realistic offline selves to the flawless, filtered, and edited online versions of others, which can be detrimental to mental well-being and perception of self.

Estimates of HE are derived from estimates of alcoholic cirrhosis, which can range from 8 percent to 20 percent (Bellentani et al. 1997; Mann et al. 2003; Sorensen et al. 1984). Mild HE occurs in up to 80 percent of cirrhotic patients, and overt HE occurs in up to 45 percent of cirrhotic patients (Bajaj 2008; Poordad 2007). One study estimated the incidence of CPM at 0.5 percent among the general population (Newell and Kleinschmidt-DeMasters 1996). However, prevalence is much higher (30 percent) among patients with liver transplants (Singh et al. 1994). For ACD prevalence, reports based on postmortem evaluation range from as low as 0.4 percent to as high as 42 percent of alcoholics (Riethdorf et al. 1991; Scholz et al. 1986; Stork 1967; Torvik and Torp 1986). Rates of ARD can depend on the setting, with facilities specializing in early identification and treatment of memory disorders reporting rates of 3 percent (McMurtray et al. 2006) and nursing homes reporting rates as high as 24 percent (Carlen et al. 1994; Oslin and Cary 2003; Ritchie and Villebrun 2008).