1Throughout this article, the term “alcohol abuse” is used to describe any type of alcohol consumption that causes social, psychological, or physical problems for the drinker. Thus, the term encompasses the clinical diagnoses of alcohol abuse and alcohol dependence as defined by the American Psychiatric Association. When alcohol consumption is abruptly http://art-times.ru/news/2357/teatr_rossiyskoy_armii_otkril_noviy_sezon.html reduced or discontinued, a withdrawal syndrome may follow, characterized by seizures, tremor, hallucinations, insomnia, agitation, and confusion (Metten and Crabbe 1995). Scientists postulate that this syndrome represents the hyperactivity of neural adaptive mechanisms no longer balanced by the inhibitory effects of alcohol (see figure).
Both dopaminergic and nondopaminergic neurons also carry dopamine receptors that are located on the nerve terminals outside the synapse (i.e., are extrasynaptic). Dopamine that has been released from a nerve terminal into the synaptic cleft can travel out of the synapse into the fluid surrounding the neurons and activate these extrasynaptic receptors. 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. More research is needed to determine how and under what drinking conditions alcohol consumption is affected by different serotonin receptor antagonists.
Thus, it is possible that electrically stimulated dopamine release could be due to several effectors beyond depolarization of the dopamine terminal. Indeed, a major role for nAChRs on dopamine terminals in regulating dopamine release has been demonstrated in rodents [53,54,55,56,57]. https://bigbars.ru/bb8801.html This disynaptic mechanism involves acetylcholine released from cholinergic interneurons activating nAChRs on dopamine axons to induce dopamine release. Thus, any changes to cholinergic signaling in striatum might also influence changes in dopamine release.
In a healthy functioning brain, only a certain amount of dopamine is released, and they rarely fill all of the dopamine receptors that are available. If too much dopamine is released, the brain effectively shuts off dopamine receptors as a way to control the flow of the chemical. 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.
We further explored the effect of long-term ethanol consumption on striatal cholinergic systems by examining gene expression of several nAChR subunits (α4, α5, α7, and β2) and markers for cholinergic interneurons (ChAT and vAChT). We found no significant differences in ChAT or vAChT expression between control and alcohol treated subjects, suggesting that long-term alcohol consumption does not adversely affect cholinergic interneurons. Similarly, we did not see any significant changes in mRNA levels of the nAChR subunits. This may be due to the ubiquitous expression of nAChRs in the striatum which would limit our ability to detect changes in specific cell types. Indeed, our analysis of dopamine transient dynamics revealed faster dopamine uptake in caudate and putamen of alcohol-consuming female, but not male, macaques. Thus, any apparent dopamine uptake differences in the male macaque groups presented here are a function of faster clearance times due to decreased dopamine release and not faster dopamine clearance rates per se.
Evidence suggests that the brain attempts to restore equilibrium after long-term alcohol ingestion (see figure). For example, although short-term alcohol consumption may increase GABAA receptor function, prolonged drinking has the opposite effect https://www.zeldalegacy.net/page/4/ (Mihic and Harris 1995; Valenzuela and Harris 1997). This decrease in GABAA function may result from a decrease in receptor levels or a change in the protein composition of the receptor, leading to decreased sensitivity to neurotransmission.
Reinforcement appears to be regulated by the interaction of multiple neurotransmitter and neuromodulatory systems. Among the neurotransmitter systems linked to the reinforcing effects of alcohol are dopamine, endogenous opiates (i.e., morphinelike neurotransmitters), GABA, serotonin, and glutamate acting at the NMDA receptor (Koob 1996). Complex interactions between these neurotransmitter systems are likely to be important for the development and maintenance of alcohol-seeking behaviors. For example, alcohol has been shown to activate dopamine systems in certain areas of the brain (i.e., the limbic system) through an interaction with glutamate receptors (Koob 1996). Moreover, dopamine systems appear to be inhibited after alcohol withdrawal, and this inhibition can be reversed by alcohol consumption (Koob 1996).
As part of a collaborative effort examining the effects of long-term alcohol self-administration in rhesus macaques, we examined DS dopamine signaling using fast-scan cyclic voltammetry. We found that chronic alcohol self-administration resulted in several dopamine system adaptations. Most notably, dopamine release was altered in a sex- and region-dependent manner. Following long-term alcohol consumption, male macaques, regardless of abstinence status, had reduced dopamine release in putamen, while only male macaques in abstinence had reduced dopamine release in caudate. In contrast, female macaques had enhanced dopamine release in the caudate, but not putamen. Dopamine uptake was also enhanced in females, but not males (regardless of abstinence state).