Alcohol’s effects on endogenous opioids and the mesolimbic dopamine system. The activity of the dopamine-releasing (i.e., dopaminergic) neurons in the ventral tegmental area (VTA) is controlled by γ−aminobutyric acid (GABA)-releasing (i.e., GABAergic) neurons. When these GABA neurons are activated (e.g., through the actions of the excitatory neuro-transmitter glutamate), their signals decrease the firing of dopaminergic neurons. Endogenous opioids, however, can act on µ receptors on the GABAergic neurons, thereby inhibiting GABA transmission, and ultimately leading to increased dopamine release. A) Acute alcohol can induce β-endorphin release, resulting in activation of µ receptors on the GABAergic neurons in VTA. This, in combination with alcohol’s inhibition of glutamate effects on GABA neurons, could lead to decreased GABAergic activity in the VTA, and subsequently increased firing of the dopaminergic neurons, resulting in increased dopamine release in the nucleus accumbens (NAc). Alcohol also directly increases the activity of dopamine neurons. B) During withdrawal from alcohol, after chronic alcohol exposure that produces alcohol dependence (i.e., in the absence of alcohol in a dependent individual), glutamate input to GABA neurons is increased, leading to decreased dopamine release. In addition, the activity of the VTA dopamine neurons is reduced. C) When alcohol is reintroduced, the dopamine neurons are more sensitive to alcohol’s direct effects; moreover, alcohol again inhibits glutamate β-endorphin release, thereby reversing the decreased dopamine release that occurs in the alcohol-abstinent, alcohol-dependent individual.
NOTE: Other systems that interact with alcohol to control dopamine neuron activity in the VTA (and dopamine release in the nucleus accumbens), but that are not shown in this figure, include endogenous cannabinoids (which can affect GABA release and interact with opioid systems), nicotinic cholinergic receptors, and serotonin transmission.
SOURCE: Clapp, P.; Bhave, S.V.; and Hoffman, P.L. How adaptation of the brain to alcohol leads to dependence: A pharmacological perspective. Alcohol Research & Health 31(4):310–339, 2008.
Download this file as a PDF
Updated: October 2009