The Effects of Long Chain-Length n-Alcohols on the Firing Frequency of Dopaminergic Neurons of the Ventral Tegmental Area

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Abstract
The dopaminergic neurons of the ventral tegmental area (DA VTA neurons) have been implicated in the reinforcing properties of drugs of abuse, including ethanol (ethyl alcohol). Ethanol increases the spontaneous firing frequency of DA VTA neurons in vitro, in both brain slices and acutely dissociated neurons, and also in vivo. In many systems, longer n-alkyl alcohols have a more potent effect than ethanol, and the potency is a function of the number of carbons in the alkyl chain. We studied n-alcohols of chain length 1 (methanol) to 5 (pentanol) on the firing rate of DA VTA neurons in brain slice preparations. All of the alcohols studied produced increases in the spontaneous firing frequency in DA VTA neurons; as the chain length increased, lower concentrations of the alcohols were needed to produce the same percentage increase in firing. With very high concentrations of all the alcohols except methanol, we observed apparent depolarization block of firing. In addition, trichloroethanol (TCE), the active metabolite of chloral hydrate, increased the firing frequency of DA VTA neurons, and the EC40 (concentration to produce a 40% increase in firing rate) of TCE was below that of ethanol. These studies indicate that excitation of VTA dopamine neurons by n-alcohols is related to the chain length of the carbons. This is likely to be a characteristic of the ethanol-sensitive element of DA VTA neurons and may be useful in identifying the element of the membrane that is responsible for ethanol-induced excitation.