The dopamine system and alcohol dependence PMC

Alcohol exposure alters several aspects of serotonergic signal transmission in the brain. For example, alcohol modulates the serotonin levels in the synapses and modifies the activities of specific serotonin receptor proteins. Abnormal serotonin levels within synapses may contribute to the development of alcohol abuse, because some studies have found that the levels of chemical markers representing serotonin levels in the brain are reduced in alcoholic humans and chronically alcohol-consuming animals.

The Neuroscience of Emotions: Clinical Relevance for Understanding Depression, Anxiety, and Addiction

These studies found that P rats have fewer 5-HT1A receptor molecules than do NP rats (DeVry 1995). Neuroimaging studies have also dramatically advanced our understanding of the brain’s response to alcohol and the neurochemical basis of alcohol dependence. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) use radiotracers that bind specifically to key receptors of interest, to quantify receptor location and availability. Neurotransmitter release can also be indirectly quantified using PET, through measurement of the amount of tracer that is ‘displaced’ from the receptor when endogenous neurotransmitter is released in response to a pharmacological (or other) challenge. Such techniques have been instrumental in the investigation of key neurotransmitter systems and identification of molecular dysfunction in the human brain. The use of PET to study the effects of chronic alcohol consumption has advanced our understanding of reward mechanisms, neuroadaptations resulting from chronic use that led to tolerance and withdrawal and has identified key regions and circuits implicated in loss of control and motivation to drink.

The dopamine system: a potential treatment target for alcohol dependence

She single-handedly inspired me to undertake this task and the work would not have borne fruition without her support and guidance. Thanks are also due to my mother, Dr. Sharmila Banerjee, without whose support and editorial help, I could not have had the will to complete this work. Furthermore, I would like to state that no financial aid in any form was received for undertaking this work. It is classified as a catecholamine (a class of molecules that serve as neurotransmitters and hormones). It is a monoamine (a compound containing nitrogen formed from ammonia by replacement of one or more of the hydrogen atoms by hydrocarbon radicals).

• A series of human imaging studies over the last decade have demonstrated that alcohol [93, 94] as well as other drugs of abuse [95] increase striatal dopamine release.
• Nonetheless, altered dopamine kinetics or release could affect dopamine-dependent synaptic plasticity [42] that might subsequently affect new learning and behavioral flexibility.
• This underscores the need to examine sex- and gender-related alterations on brain function and structure in alcohol use; improving our understanding of these effects may enable tailoring of pharmacotherapeutic treatments to improve outcomes.
• Serotonin’s actions at the synapses normally are tightly regulated by proteins called serotonin transporters, which remove the neurotransmitter from the synaptic cleft after a short period of time by transporting it back into the signal-emitting cell.
• There are conflicting reports in this regard with different population groups having different alleles as risk factors.

Alcohol and the brain: from genes to circuits

The reticular activating system is an area in the brainstem that controls consciousness, alcohol can dampen this system. Recently mutations in the SERT gene, commonly known as 5’- hydroxtryptamine transporter linked polymorphic region (5’-HTTLPR), has been implicated in cases of alcoholism. One mutation is known as the “long” allele and the other mutation is known as the “short” allele. The difference between the two alleles is that the “short” version of the allele has a 44 bp deletion in the 5’ regulatory region of the gene. This 44 bp deletion occurs 1 kb upstream from the transcription initiation site of the gene.[53] This is depicted through the following diagram [Figure 4]. Alcohol addiction and dependence of late has been shown to be affected by the influence of genes.

• Increased 5-HT3 activity results in enhanced GABAergic activity, which, in turn, causes increased inhibition of neurons that receive signals from the GABA-ergic neurons.
• In addition, researchers must investigate whether the effects of these drugs vary among subgroups of alcoholics (e.g., alcoholics with different drinking patterns or with co-occurring mental disorders).
• Thus, one approach researchers currently are pursuing to develop better therapeutic strategies for reducing alcohol consumption focuses on altering key components of the brain’s serotonin system.
• The study found that when compared with healthy controls, patients with pure AD had a significantly lower availability of SERT in the midbrain.
• Any interference with serotonin transporter function extends or diminishes the cells’ exposure to serotonin, thereby disrupting the exquisite timing of nerve signals within the brain.

Your brain doesn’t want you to stop drinking after a few drinks, even when your dopamine levels start to deplete. Both your brain and body are chasing that feeling caused by the increased level of dopamine and you are now essentially hooked. This is where fun night out runs the risk of leading to an addiction for some heavy drinkers while for others it has no effects at all. Studies show that men create an increased amount of dopamine compared to women which more than likely contributes to men’s increased likeliness to become addicted to alcohol over women. Alcohol-induced changes in brain functions can lead to disordered cognitive functioning, disrupted emotions and behavioral changes.

4. Resting State Functional Connectivity

Other serotonin-activated receptors (i.e., the 5-HT3 receptors) double as ion channels. 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. The metabolism of alcohol itself can also lead directly to neurotoxicity as the metabolite acetaldehyde is toxic and can lead to neurodegeneration. Finally, alcohol can lead to neurotoxicity via the induction of both the central and peripheral immune system, causing damaging levels of inflammation.

Alcohol has such a wide variety of effects, affecting the parts of your brain that control speech, movement, memory, and judgment. This is why the signs of overindulgence include slurred speech, bad or antisocial behavior, trouble walking, and difficulty performing manual tasks. Short Term Memory Loss – Alcohol affects the limbic system which controls emotions and memory so the loss of dopamine isn’t the only reason for your seemingly unwarranted emotional outbursts.

A series of experiments in outbred rats show that the dopamine stabilizer OSU6162 attenuates several alcohol‐mediated behaviours including voluntary alcohol intake, alcohol withdrawal symptoms and cue/priming‐induced reinstatement of alcohol seeking in long‐term drinking rats [196]. Furthermore, OSU6162 blunted alcohol‐induced dopamine output in the NAc of alcohol‐naïve rats [196], indicating that OSU6162 has the ability to attenuate the rewarding effects of alcohol. In contrast, a more recent microdialysis study conducted in long‐term drinking rats, showed that OSU6162, compared to vehicle‐pretreatment, had no significant effect on the alcohol‐induced dopamine peak [29]. The contrasting microdialysis results in alcohol‐drinking versus alcohol‐naïve rats highlight OSU6162´s ability to modulate the dopamine output dependent on the prevailing dopaminergic tone. Furthermore, these results indicate that OSU6162 might have the ability to attenuate alcohol‐mediated behaviours by counteracting the hypo‐dopaminergic state induced by long‐term drinking. The dopamine deficiency hypothesis is supported by a study showing decreased dopamine receptor gene expression after several months of voluntary alcohol drinking [103].

Demographic and psychometric data

Intriguingly, alcohol markedly perturbs the synaptic spliceosome in the cortex of mice, thereby affecting the local translation of proteins involved in synaptic function [38]. These changes are particularly pronounced does alcohol produce dopamine following repeated exposure to alcohol and were proposed to regulate sensitization [38]. The detailed necropsy procedures used to harvest tissues [28] and obtain ex vivo slices [8] have been previously described.