Alcohol
Volume 23, Issue 3 , Pages 131-139, April 2001

Effects of ethanol on the dorsal raphe nucleus and its projections to the caudate putamen☆

Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Dr., Indianapolis, IN 46202-4887, USA

Received 2 October 2000; received in revised form 3 January 2001; accepted 15 January 2001.

Abstract 

The objective of this study was to examine the effects of intraperitoneal injection of ethanol on the activity of the dorsal raphe nucleus (DRN) serotonin (5-hydroxytryptamine [5-HT]) system and its projections to the rostral caudate putamen (CPu) and determine whether rapid tolerance to the effects of ethanol develops in this system. Adult, male, Wistar rats were used in these experiments. In experiment 1, a microdialysis procedure was used to determine (a) the effects of acute intraperitoneal administration of ethanol (1.75 and 2.5 g/kg) on the extracellular levels of 5-HT in the rostral CPu and (b) whether rapid tolerance develops to these effects. In experiment 2, firing rates of 5-HT neurons were determined in the DRN after intraperitoneal administration of 2.5 g/kg of ethanol. The results of the microdialysis experiments indicated that the 2.5-g/kg dose significantly (P<.005) increased the extracellular levels of 5-HT to 150%–160% of baseline. Compared with findings for rats pretreated with saline 24 h earlier, prior treatment 24 h earlier with 2.5 g/kg of ethanol had no effect on the extracellular levels of 5-HT produced by a challenge dose of 2.5 g/kg of ethanol. Contrary to the effects in the CPu, intraperitoneal administration of 2.5 g/kg of ethanol significantly (P<.005) decreased the firing rates of 5-HT neurons in the DRN to approximately 50% of control. Overall, the results suggest to us that there is a dissociation between the effects of acute administration of ethanol on 5-HT cell body neuronal activity and 5-HT synaptic activity. The higher extracellular levels of 5-HT in the CPu may be due to increased release of 5-HT from a direct or an indirect action of ethanol, a result of inhibiting 5-HT reuptake, or related to both of these mechanisms. In addition, the findings suggest to us that rapid tolerance did not develop to the effects of ethanol on the 5-HT system within the CPu.

Keywords:  Dorsal raphe nucleus, Caudate putamen, Acute ethanol, Serotonin, Microdialysis, Firing rates

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☆ A paper published as a high-priority communication is one that reviewers have identified as being of high scientific significance and have recommended that the study findings should be communicated to the scientific community as soon as possible.Editor: T.R. Jerrells

PII: S0741-8329(01)00126-4

Alcohol
Volume 23, Issue 3 , Pages 131-139, April 2001

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