Researchers at McGill University in Canada performed positron emission tomography (PET) brain scans on 26 social drinkers and noted a “distinctive brain response” in the higher-risk subjects after they consumed three alcoholic drinks. 3By breeding rats with similar alcohol-consumption patterns (e.g., high consumption or low consumption) with each other for several generations, researchers created two strains with distinctly different preferences for alcohol. If you drink for long periods of time, it can cause depression, and when you abruptly stop drinking, it can cause anxiety,” says Dr. Anand. There’s also more of an effect on your brain and its development if you’re younger — one that can have a lasting impact. These effects can happen even after one drink — and increase with every drink you have, states Dr. Anand. But as you drink more — and you don’t need to drink that much more — eventually, the enzymes that break down the alcohol get saturated.
Consequently, alcohol’s effects on serotonin may alter the activity of GABAergic neurons in the hippocampal formation. These changes may disrupt cognition and possibly contribute to alcohol-induced memory loss and impaired judgment. Serotonin (5-HT) can bind to receptors that activate proteins within the cell called G proteins. Activation of these proteins, in turn, affects ion channels in the cell membrane and induces the formation of signaling molecules (i.e., second-messenger molecules).
What Is Dopamine?
Serotonin is produced in and released from neurons that originate within discrete regions, or nuclei, in the brain (Cooper et al. 1991). Many serotonergic neurons are located at the base of the brain in an area known as the raphe nucleus, which influences brain functions related to attention, emotion, and motivation. The axons of the neurons in the raphe nucleus extend, or project, throughout the brain to numerous regions with diverse functions. These brain regions include the amygdala, an area that plays an important role in the control of emotions, and the nucleus accumbens, a brain area involved in controlling the motivation to perform certain behaviors, including the abuse of alcohol and other drugs. In these brain regions, the axon endings of the serotonergic neurons secrete serotonin when activated.
Through this mechanism, dopamine modulates the neurotransmitter release that is induced by cellular excitation (i.e., neurotransmitter secretion). For example, activation of some extrasynaptic D2-family receptors can inhibit the release of dopamine itself, thereby reducing dopaminergic signal transmission. Serotonin may interact is mixing cymbalta and alcohol safe with GABA-mediated signal transmission by exciting the neurons that produce and secrete GABA (i.e., GABAergic neurons). For example, serotonin can increase the activity of GABAergic neurons in the hippocampal formation (Kawa 1994), a part of the brain that is important for memory formation and other cognitive functions.
To date, the exact mechanisms underlying the changes in serotonin-metabolite levels are still unknown. Long-term, or chronic, alcohol exposure2 can lead to adaptive changes within brain cells. This process, also called tolerance development, presumably is a mechanism to reestablish normal cell function, or homeostasis, in response to continuous alcohol-induced alterations. Thus, the number of 5-HT2 receptor molecules and the chemical signals produced by the activation of this receptor increase in laboratory animals that receive alcohol for several weeks. The neurons then store the dopamine in small compartments (i.e., vesicles) in the terminals of their axons.
When discussing the consequences of alcohol’s actions on the brain, researchers frequently use terms such as motivation, reinforcement, incentives, and reward. Schematic representation of the major dopaminergic systems (viewed from the top of the head). The nigrostriatal system originates in the A9 cell group and extends to the dorsal striatum, which includes the caudate nucleus and putamen (CPU). The mesolimbic system originates primarily in the A10 cell group and extends to the ventral striatum, which includes the nucleus accumbens (NAc) and the olfactory tubercle (OT). The mesocortical system also originates primarily in the A10 cell group and affects various regions of the cerebral cortex.
1The term “dopaminergic” refers to both the neurons and the signaling processes that use dopamine. Dopaminergic neurons reach not only the NAc, but also other areas of the extended amygdala as well as parts of the septo-hippocampal system. Consequently, dopamine acts at multiple sites to control the integration of biologically relevant information that determines motivated responding.
How Does Alcohol Affect Your Brain?
Alcohol interacts with serotonergic synaptic transmission in the brain in several ways. Even single-episode (i.e., acute) alcohol exposure alters various aspects of serotonin’s synaptic functions. In humans, for example, the levels of serotonin metabolites in the urine and blood increase after a single drinking session, indicating increased serotonin release in the nervous system (LeMarquand et al. 1994a). For example, increased serotonin release after acute alcohol exposure 52 ways to identify a covert narcissist has been observed in brain regions that control the consumption or use of numerous substances, including many drugs of abuse (McBride et al. 1993). Researchers currently are trying to determine the exact mechanisms underlying the alcohol-induced changes. For example, they are investigating whether the net increase in synaptic serotonin levels results from alcohol’s direct actions on molecules involved in serotonin release and uptake or from more indirect alcohol effects.
- Specifically, prefrontal regions involved in executive functions and their connections to other brain regions are not fully developed in adolescents, which may make it harder for them to regulate the motivation to drink.
- This dopamine release may contribute to the rewarding effects of alcohol and may thereby play a role in promoting alcohol consumption.
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- Serotonin may interact with GABA-mediated signal transmission by exciting the neurons that produce and secrete GABA (i.e., GABAergic neurons).
Researchers currently cannot directly measure serotonin concentrations in the human brain or within the synapses in laboratory animals. To gain information about serotonin levels in the brain, physicians and researchers have measured the concentrations of serotonin breakdown products generated after the neurotransmitter has been removed from the synapse (i.e., serotonin metabolites). Together, medication and behavioral health treatments can facilitate functional brain recovery. A huge risk factor for people who develop alcohol use disorder is early-onset drinking. So, if you drink before the age of 14, there’s about a 50% chance you’re going to develop an alcohol use disorder in your adulthood,” explains Dr. Anand.
This receptor is present in many brain regions (Grant 1995) and may reside on GABAergic neurons. 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. Consequently, alcohol’s effects on these receptor subtypes also might influence GABAergic signal transmission in the brain. Other drugs that affect serotonergic signal transmission also alter alcohol consumption in animals (LeMarquand et al. 1994b). For example, antagonists of the 5-HT3 and 5-HT1A receptors reduced alcohol ingestion in rodents (Litten et al. 1996; Pettinati 1996; DeVry 1995).
Serotonin Levels in Alcoholics
The alcoholics also reported less desire to drink and fewer pleasurable feelings after drinking. Fluoxetine reduces alcohol consumption in humans only moderately, however, and does not affect all alcoholics (Litten et al. 1996). Moreover, although increased serotonin levels at the synapses in the brain can moderate alcohol consumption, additional factors contribute to continued alcohol abuse.
For example, recent evidence indicates that buspirone—an agent that binds to the 5-HT1A receptor and which is used as an anxiety-reducing (i.e., anxiolytic) medication—also increases the time of abstinence from heavy drinking (Litten et al. 1996; Pettinati 1996). These findings suggest that buspirone may help reduce anxiety in alcoholics with anxiety disorders, thereby possibly improving their compliance with therapeutic regimens. 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. Consequently, serotonin can affect neighboring neurons only for a short period of time. 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. The net result of such disruptions is abnormal brain activity, which can lead to psychological problems or mental illness.
Alcohol’s Actions as a Reinforcer: Dopamine’s Role
Second messengers also can act on ion channels or travel to the nucleus to alter gene expression. Other serotonin-activated receptors (i.e., the 5-HT3 receptors) double as ion channels. The binding of serotonin to its receptors initiates a series of biochemical events a potential case of acute ketamine withdrawal that converts the extracellular, chemical signal into an intracellular signal in the recipient cell. For example, the interaction of serotonin with one type of receptor stimulates the formation of small molecules (i.e., second messengers) within the cell.