Organic certification for Alcoholic

Courtesy: Organic certification for Alcoholic

Rewarding and reinforcing actions

The reinforcing effects of alcohol consumption are mediated by acetaldehyde generated by catalase and other oxidizing enzymes such as cytochrome P-4502E1 in the brain. Although acetaldehyde has been associated with some of the adverse and toxic effects of ethanol, it appears to play a central role in the activation of the mesolimbic dopamine system.

Ethanol’s rewarding and reinforcing (i.e., addictive) properties are mediated through its effects on dopamine neurons in the mesolimbic reward pathway, which connects the ventral tegmental area to the nucleus accumbens (NAcc). One of ethanol’s primary effects is the allosteric inhibition of NMDA receptors and facilitation of GABA_A receptors (e.g., enhanced GABA_A receptor-mediated chloride flux through allosteric regulation of the receptor). At high doses, ethanol inhibits most ligand-gated ion channels and voltage-gated ion channels in neurons as well.

With acute alcohol consumption, dopamine is released in the synapses of the mesolimbic pathway, in turn heightening activation of postsynaptic D₁ receptors. The activation of these receptors triggers postsynaptic internal signaling events through protein kinase A, which ultimately phosphorylate cAMP response element binding protein (CREB), inducing CREB-mediated changes in gene expression.

With chronic alcohol intake, consumption of ethanol similarly induces CREB phosphorylation through the D₁ receptor pathway, but it also alters NMDA receptor function through phosphorylation mechanisms; an adaptive downregulation of the D₁ receptor pathway and CREB function occurs as well. Chronic consumption is also associated with an effect on CREB phosphorylation and function via postsynaptic NMDA receptor signaling cascades through a MAPK/ERK pathway and CAMK-mediated pathway. These modifications to CREB function in the mesolimbic pathway induce expression (i.e., increase gene expression) of ΔFosB in the NAcc, where ΔFosB is the “master control protein” that, when overexpressed in the NAcc, is necessary and sufficient for the development and maintenance of an addictive state (i.e., its overexpression in the nucleus accumbens produces and then directly modulates compulsive alcohol consumption).

Relationship between concentrations and effects

Recreational concentrations of ethanol are typically in the range of 1 to 50 mM. Very low concentrations of 1 to 2 mM ethanol produce zero or undetectable effects except in alcohol-naive individuals. Slightly higher levels of 5 to 10 mM, which are associated with light social drinking, produce measurable effects including changes in visual acuity, decreased anxiety, and modest behavioral disinhibition. Further higher levels of 15 to 20 mM result in a degree of sedation and motor incoordination that is contraindicated with the operation of motor vehicles. In jurisdictions in the United States, maximum blood alcohol levels for legal driving are about 17 to 22 mM. In the upper range of recreational ethanol concentrations of 20 to 50 mM, depression of the central nervous system is more marked, with effects including complete drunkenness, profound sedation, amnesia, emesis, hypnosis, and eventually unconsciousness. Levels of ethanol above 50 mM are not typically experienced by normal individuals and hence are not usually physiologically relevant; however, such levels – ranging from 50 to 100 mM – may be experienced by alcoholics with high tolerance to ethanol. Concentrations above this range, specifically in the range of 100 to 200 mM, would cause death in all people except alcoholics