23-09-2021

Different brain circuits are responsible for coordinating and performing specific functions. Networks of neurons send signals back and forth to each other and among different parts of the brain, the spinal cord, and nerves in the rest of the body (the peripheral nervous system). Instead of electrical circuits on the silicon chips that control our electronic devices, the brain consists of billions of cells, called neurons, which are organized into circuits and networks.

• This begins to change how a person perceives natural rewards like eating or watching a great movie.
• What happens in addiction is that, through completely natural processes involved in all learning, the brain prunes nerve pathways of attention and motivation to preferentially notice, focus on, desire, and seek the substance.
• Microglial activation has also been investigated in response to heavy session intermittent drinking in rodents [93].
• Although inconsistencies exist in the literature, the cumulative evidence presently available suggests that alcohol consumption increases the release of endogenous opioid peptides and that μ- and δ-receptors facilitate the relationship between alcohol consumption and reward.
• The metabolism of alcohol itself can also lead directly to neurotoxicity as the metabolite acetaldehyde is toxic and can lead to neurodegeneration.
• Original concepts of brain structure modification were unidirectional—that is, degradation occurred with age or disease without the chance of neuronal regeneration.

Whether it’s alcohol, prescription pain pills, nicotine, gambling, or something else, overcoming an addiction isn’t as simple as just stopping or exercising greater control over impulses. It was once thought that surges of the neurotransmitter dopamine produced by drugs directly caused the euphoria, but scientists now think dopamine has more to do with getting us to repeat pleasurable activities (reinforcement) than with producing pleasure directly. But an explosion of knowledge and technology in the field of molecular genetics has changed our basic understanding of addiction drastically over the past decade.

Adolescence, Brain Change, and Vulnerability to Substance Use Disorders

Early case studies highlighted striking morphological anomalies, most notably thinning of the corpus callosum and enlargement of ventricles, but subsequent radiological investigations have highlighted there is considerable variability in the impact of FASD on brain development [58]. Quantitative analyses of alcohol vs drugs brain macrostructure in FASD have repeatedly found lower grey and white matter volume along with increased thickness and density of cortical grey matter [59]. Crucially, findings have found no morphological differences in the occipital lobe, suggesting that not all brain structures are affected equally.

Instead of stigmatizing addiction, it’s possible to move forward by increasing understanding of drug use on the brain and highlighting how addiction is treatable. The avoidance of withdrawal symptoms can partially explain why it can be especially difficult for people to stop taking drugs on their own. People who regularly misuse a drug or alcohol may find that they feel sick or experience other uncomfortable withdrawal symptoms when they stop using the substance suddenly. They are found naturally (in marijuana or cannabis), but may also be laboratory-made (synthetic cannabinoids, Spice/K2).

Neuropsychological Sequelae of Alcoholism

Drivers with a BAC of 0.08 or more are 11 times more likely to be killed in a single-vehicle crash than non-drinking drivers. Some states have higher penalties for people who drive with high BAC (0.15 to 0.20 or above) due to the increased risk of fatal accidents. Thiamine requires phosphorylation by thiamine pyrophosphokinase to be converted to its active co-enzyme form.

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]. Activated GABA receptors inhibit, or decrease the firing of individual neurons, and GABA signaling is critical to maintaining a healthy level of brain activity. Insufficient levels of GABA can cause restlessness, insomnia, anxiety, and seizures due to abnormally high levels of neural overactivity. The brain’s system of endorphins and opioid receptors are survival tools that help people in dangerous situations from being overcome by pain or fatigue. Medically, opioids are an important treatment for people who have severe pain that cannot be controlled with other medications.

What Are the Short-Term and Long-Term Effects of Drug Use on the Brain?

However, the extent of alcohol induced microglial activation may well be dependent on the extent and pattern of alcohol exposure. Recent studies conducted in CeA slices showed that the alcohol-induced increase of GABAergic transmission was larger in mice without a functional δ-receptor gene (i.e., δ-receptor knockout mice). In addition, a δ-receptor inverse agonist, which binds to the same binding site as an agonist but exerts the opposite effect, augmented alcohol actions on GABAergic response in control mice to a level comparable with alcohol effects seen in δ-receptor knockout mice (Kang-Park et al. 2007). This result supports the hypothesis that endogenous opioid peptides modulate the alcohol-induced augmentation of GABAA receptor–dependent circuitry in the CeA (Roberto et al. 2003).

• Ethanol also differentially affects the excitability of neurons that are not tonically active.
• These studies (Roberto et al., preliminary data) showed that superfusion of the CB1 agonist WIN onto CeA neurons markedly reduced GABA transmission (see figure 3).
• Nerve cells, or neurons, allow different parts of the body to communicate with each other by receiving, conducting, and transmitting electrical charges (i.e., impulses) throughout the nervous system.
• For example, acute ethanol application blocks LTP (Figure 2U) and has diverse effects on LTD (Clarke and Adermark, 2010; McCool, 2011; Yin et al., 2007).
• Below the brain is the cerebellum, which is comprised of tissues that coordinate movement.
• This part of the brain regulates decisions, choices, and the ability to know the difference between right and wrong.

Neuroscientists now know that some abused substances block reabsorption, leaving too much neurotransmitter around. Although many neurotransmitters and chemicals that act like them have been identified, those most notably linked to addiction are norepinephrine, dopamine, serotonin, substance P, and gamma-aminobutyric add (GABA). Neurotransmitters circulate, collect, and act at specific sites on nearby cell surfaces called receptor proteins, each of which is shaped to fit and receive a particular neurotransmitter and bind it the way a lock “recognizes” a key. Only after a neurotransmitter binds can the signal it carries travel to the next cell. If the cell is flooded with too much neurotransmitter, an elegant “control” system is normally activated so that the cell reabsorbs the excess for later use.

KEY TERMS

This review focuses on alcohol, opioids, and cannabinoids because these drugs only recently have been shown to interact at GABAergic synapses in the CeA. In addition, the authors are familiar with these drugs and were able to report on data generated in their laboratories. Because there are no receptors or well-defined transduction mechanisms for alcohol, the authors emphasize the cellular mechanisms affected by alcohol.

• “Intoxication occurs when alcohol intake exceeds your body’s ability to metabolize alcohol and break it down,” explains Amanda Donald, MD, a specialist in addiction medicine at Northwestern Medicine.
• As a group, alcoholics share this constellation of behaviors characteristic of frontal lobe dysfunction, which also can include impaired judgment, blunted affect, poor insight, distractibility, cognitive rigidity, and reduced motivation.
• Presynaptic ethanol effects at some synapses are secondary to release of neuromodulators that are themselves the direct mediators of increased vesicle fusion.
• This learned “reflex” can last a long time, even in people who haven’t used drugs in many years.
• Synthetic cathinones, more commonly known as “bath salts,” target the release of dopamine in a similar manner as the stimulant drugs described above.

It is worth noting that the function of many molecules in mammalian neurons appears to be remarkably insensitive to ethanol (Yamakura et al., 2001). Thus, earlier ideas about ubiquitous molecular effects due to changes in membrane fluidity are not helpful in understanding how ethanol alters neuronal function (Peoples et al., 1996). Even if fluidity changes occur, these changes lead to altered neuronal function, and thus, we must examine the proteins that dictate neuronal function. Thankfully, the tools available to modern neuroscientists have enabled examination of ethanol effects at multiple levels. We can now determine how a given molecular effect on a specific neuronal or synaptic subtype contributes to ethanol-induced behavioral changes.