It is now clear that dopamine neurons are heterogeneous, and recent reports have identified a subset of VTA dopamine neurons with greater sensitivity to ethanol’s effects (Avegno et al., 2016; Mrejeru et al., 2015; Tateno and Robinson, 2011) (Figures 2A and 2D). The chronic and withdrawal effects of ethanol on dopamine neuron firing are mixed, with decreases observed in anesthetized rats (Diana et al., 1996) but no change (Okamoto et al., 2006; Perra et al., 2011) or increases (Didone et al., 2016) detected in slices. 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). Thus, while changes in dopamine neuron firing are among the most consistent effects of ethanol, more work is needed to pin down the mechanisms underlying this effect. Chronic alcohol consumption can lead to lasting changes in brain structure and function.
These effects occur in the hippocampus (Lovinger et al., 1990) (Figure 2Q), frontal cortex (Weitlauf and Woodward, 2008), and CeA (Kirson et al., 2017; Roberto et al., 2004b, 2006; Zhu et al., 2007) (Figure 2R), among other brain regions. Indirect ethanol targets include ion channel subunits, intracellular signaling proteins, growth factors, transcription factors, proteins involved in epigenetic regulation of gene expression, and even membrane lipids. In most cases, there is no clear evidence of an ethanol-binding site or that acute ethanol alters the expression or function of these molecules, but they show prominent alterations following chronic ethanol exposure and intake.
Alcoholism and the Brain: An Overview
For example, structural MRI can clearly delineate gray matter from white matter but cannot detect damage to individual nerve fibers forming the white matter. Moreover, the findings correlate with behavioral tests of attention and memory (Pfefferbaum et al. 2000). These nerve pathways are critically important because thoughts and goal-oriented behavior depend on the concerted activity of many brain areas.
Ethanol alters learning and memory (Oslin and Cary, 2003; White, 2003), and this may involve effects on synaptic plasticity, including long-term depression (LTD) and long-term potentiation (LTP) (reviewed in Zorumski et al., 2014). Most of the data on ethanol effects on synaptic plasticity come from studies in the hippocampus. Acute ethanol inhibits LTP in hippocampal slices (Blitzer et al., 1990; Morrisett and Swartzwelder, 1993), but these results are not consistent (Fujii et al., 2008; Swartzwelder et al., 1995). This variability may be due to many factors, including age, subregion, and stimulus strength.
Interestingly, acute ethanol exposure following chronic ethanol treatment has the same effect as acute ethanol in naive animals, suggesting that acute ethanol-induced facilitation of GABA transmission does not undergo tolerance (Roberto et al., 2004a) (Figure 3G). Specific groups of neurons express one or more channels that are direct or indirect ethanol targets, allowing for neuron-specific ethanol modulation of activity. In the case of neurons whose intrinsic activity is ethanol insensitive, it remains to be determined whether they lack ethanol target channels or whether the factors that control sensitivity to ethanol (e.g., post-translational modifications) differ between ethanol-sensitive and insensitive neurons.
Models Based on Characteristics of Individual Alcoholics
Cerebellar degeneration caused by alcohol occurs when neurons in the cerebellum deteriorate and die. The cerebellum is the part of the brain that controls coordination and balance. Alcoholic neuropathy occurs when too much alcohol damages the peripheral nerves. This can be permanent, as alcohol can cause changes to the nerves themselves. Deficiencies in B6 and B12, thiamine, folate, niacin, and vitamin E can make it worse.
DTI Findings in Uncomplicated Alcoholism
This is because they measure hemodynamic changes (blood flow and oxygenation), indicating the neuronal activation only indirectly and with a lag of more than a second. Yet, it is important to understand the order and timing of thoughts, feelings, and behaviors, as well as the contributions of different brain areas. Although there are no known studies using structural MRI in animal models of ACD, ARD, or MBD, the following section examines animal studies in uncomplicated alcoholism. Since the early 1980s, conventional structural MRI has allowed researchers to visualize the living human brain. Detailed images of the brain are possible in part because the different brain tissue types (i.e., gray matter, white matter, and cerebrospinal fluid CSF) contain different proportions of water (Rumboldt et al. 2010).
- The cerebellum, responsible for coordinating movement and balance, is highly susceptible to alcohol’s effects.
- Behavioral neuroscience offers excellent techniques for sensitively assessing distinct cognitive and emotional functions—for example, the measures of brain laterality (e.g., spatial cognition) and frontal system integrity (e.g., executive control skills) mentioned earlier.
- This creates a harmful cycle where drinking and mental health problems reinforce each other.
- In the following sections, we will consider the neurophysiological and behavioral effects of ethanol.
For example, the structural basis for a direct interaction of ethanol with the prototypic G. Violaceus LGIC has been determined and is thought to be a transmembrane cavity between two membrane-spanning domains (Sauguet et al., 2013). Identifying the expression sites and cellular actions of the subunits of these ethanol-sensitive channels is an important next step in understanding how the molecular effect of ethanol translates into altered neuronal and circuit function.
These in vivo MR features correspond with evidence of increased numbers of nonneuronal (i.e., glial) cells called astrocytes in basal ganglia and cerebral cortex of HE brains (Caine et al. 1997). Although discriminating features of WE and HE have been outlined, these diseases can be difficult to differentially diagnose and distinguish, because patients can appear to have similar symptoms and comparable MRI results, especially among alcoholics (Thorarinsson et al. 2011). Chronic ethanol exposure and intake also alter GABAergic transmission via pre- and postsynaptic mechanisms. These effects were covered in a recent review (Roberto and Varodayan, 2017) and will not be discussed in detail here. Both increases and decreases in GABA release are observed in several brain regions and they appear to be synapse specific (Cuzon Carlson et al., 2011; Herman et al., 2016a; Schindler et al., 2016; Tremwel et al., 1994; Wanat et al., 2009; Wilcox et al., 2014) (Figures 3E–3G). In the CeA, for example, CRF levels and GABA transmission are increased and remain so during acute withdrawal.
These findings indicate that ethanol’s effects on intrinsic excitability are region and cell-type specific. Indeed, in the globus pallidus external segment, acute ethanol decreases the firing of low-frequency, but not high-frequency, firing neurons. The ethanol-induced inhibition of low-frequency firing neurons is attributable to ethanol activation of the BK channel (Abrahao et al., 2017). Thus, this is one neuronal subtype in which the bottom-up approach can be used to assess the circuit and behavioral effects of BK activation by ethanol. Over time, excessive drinking can lead to sun rocks thc mental health problems, such as depression and anxiety.
The bright spots appear in the midbrain gray matter surrounding the cerebral aqueduct (i.e., periaqueductal gray matter), mammillary bodies, and tissue surrounding the third ventricle3 (Lenz et al. 2002; Sullivan and Pfefferbaum 2009). These findings agree with postmortem diagnosis of WE, often requiring evidence of lesions in the mammillary bodies and periventricular areas (e.g., Caine et al. 1997). In addition, observed MR hyperintense areas in WE include the thalamus, cerebellar vermis (Murata et al. 2001), dorsal medulla, tectal plates (Ha et al. 2012), olivary bodies, and dorsal pons (Liou et al. 2012). In contrast with early MR studies suggesting that KS affects the mammillary bodies while sparing the hippocampi (Squire et al. 1990), more recent work demonstrates hippocampal volume deficits in KS (Sullivan and Marsh 2003). Other regions affected by KS are the thalamus, orbitofrontal cortex (Jernigan et al. 1991b), cerebellum, and pons (Zahr et al. 2009).