Effects of Chronic Ethanol Consumption and Aging on 5-HT2A Receptors and 5-HT Reuptake Sites

The serotonergic system in brain is adversely affected by both aging and chronic ethanol consumption. The present study examined the combined effects of aging and chronic ethanol consumption on two components of the serotonergic system. Serotonin (5-HT) reuptake sites and 5-HT_2A receptors were quantitated in brain areas of 5-, 14-, and 24-month-old male Fischer 344 rats that were pair-fed a control or 6.6% (v/v) ethanol-containing liquid diet on a chronic basis. The regions examined include those containing the cell bodies and projections of serotonergic neurons. These experiments demonstrated the sensitivity of the serotonergic system of male Fischer 344 rats to both aging and chronic ethanol consumption. In control rats, aging was associated with a decline in the concentration of 5-HT_2A receptors in the nucleus accumbens and four cortical regions: frontal, parietal, piriform, and cingulate cortex. 5-HT_2A receptors were also reduced in the frontal, parietal, and cingulate cortex of aged ethanol-fed rats. In contrast, 5-HT reuptake sites were increased in older rats in the frontal cortex, nucleus accumbens, amygdala, and CA3 region of the hippocampus. If comparable changes in 5-HT_2A receptors and 5-HT reuptake sites occur in elderly humans, they may contribute to ethanol consumption, and lead to cognitive and other age-related problems. These changes may also alter the effectiveness of serotonergic drugs used in the treatment of alcoholism and mental disorders. The effects of chronic ethanol consumption were more limited. The only significant ethanol effect was an increase of 5-HT_2A receptors in the nucleus accumbens of 5-month-old ethanol-fed rats.