*2.2.3. Dopamine*

Transmission of dopamine is linked via two groups of G-protein-linked receptors: D1-like (D1 and D5 receptors) and D2-like (D2, D3 and D4 receptors). These receptors are classified on the basis of adenylatecyclase activity (stimulation or inhibition). Dopamine plays a central role in mediating alcohol compensation through mesocortical and mesolimbic pathways [29]. During chronic alcohol consumption, the release of dopamine depends on the large amount of the alcohol consumption, which gives pleasurable effect of alcohol intake. Reduction in dopamine release is observed during alcohol withdrawal. This ultimately reduces noticeable neuronal cells, leading to dysphoria and depression as a major part in the motivational and behavioral changes [30]. Chronic alcohol drinking has been reported to produce constant neurological changes in transmission of dopamine within the mesoaccumbens reward circuitry, including increased basal extracellular levels of dopamine in the NAC [31], increased firing rate in the ventral tegmental area (VTA) dopamine neurons [32] and changes in the function of dopamine receptor [33]. In comparison, withdrawal from chronic alcohol drinking due to increased dopamine uptake levels resulted in decreased VTA dopamine neuronal activity [34], and reduced basal levels of dopamine in the ventral and dorsal subregions of the striatum, possibly due to enhanced dopamine uptake [35]. The aripiprazole (D2 dopamine receptor agonist) has shown some effectiveness in treating dependence of alcohol [36].

#### *2.2.4. Serotonin*

Serotonin exerts its known role in regulating various behaviors (e.g., feeding, sleep/arousal, aggression), mood and emotional behavior [37] via several metabotropic (5-HT1 and 5-HT2 subtypes) and ionotropic (5-HT3) receptors throughout the brain depending on the consumption of alcohol [38]. Alcohol elevates serotonin release in the central nervous system (CNS) affecting emotion, temper and thoughts. The 5-HT3 receptor function is altered by ethanol consumption through its actions on receptor proteins [39]. Chronic alcohol exposure reduces serotonin levels in several brain regions [40]. Researchers have focused on the treatment for alcohol dependence and comorbid depression [41], post-stress disorder [42] and anxiety [43]. Inhibition of serotonin reuptake was done through fluoxetine. The milnacipran blocks both serotonin and norepinephrine reuptake. Both fluoxetine and milnacipran are found to be effective in reducing alcohol consumption in the rats model [44]. Consumption of alcohol (5%) every third day for 18 days leads to disturbance in serotonin function within the nucleus accumbens [45] (**Tables 2** and **3**).
