Chronic amitriptyline administration increases serotonin transporter binding sites in the hippocampus of aged rats

The effects of ageing and of chronic antidepressant treatment upon 5-HT tra nsporter sites ([H-3]paroxetine binding) in the rat hippocampus was examine d. [H-3]paroxetine binding to transporter sites was decreased with ageing i n the hippocampus of control rats (38% decrease in dentate gyrus and CA4). Amitriptyline (10 mg/kg, i.p.) had no significant effect on [H-3]paroxetine binding in 10 months old rats, but increased binding sites in 24 months ra ts in all hippocampal subregions (greatest increase of 109% in CA1 compared to saline controls). These data indicate an age-related decrease in hippoc ampal serotonin transporter sites and upregulation of these sites following 10 weeks of amitriptyline. The observed increase in transporter sites foll owing amitriptyline may contribute to the general lower effectiveness of tr icyclic antidepressants with ageing. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.