Influence of chronic dopamine transporter inhibition by RTI-336 on motor behavior, sleep and hormone levels in rhesus monkeys

• Type of Material: Article
• Authors: Monica L. Andersen, Emory University; Eileen K. Sawyer, Emory University; F. Ivy Carroll, Research Triangle Institute; Leonard Howell, Emory University
• Language: English
• Date: 2012-04
• Publisher: American Psychological Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2013 American Psychological Association
• Title of Journal or Parent Work: Experimental and Clinical Psychopharmacology
• ISSN: 1064-1297
• Volume: 20
• Issue: 2
• Start Page: 77
• End Page: 83
• Grant/Funding Information: The research was supported by USPHS Grants DA10344 (LLH), DA00517 (LLH), DA05477 (FIC), RR00165 (Yerkes National Primate Research Center), T32-DA015040 (EKS) and Associacao Fundo de Incentivo a Pesquisa (AFIP) and CNPq (MLA).
• Research Categories: Psychology, Behavioral; Chemistry, Organic

Abstract

Rationale Dopamine transporter (DAT) inhibitors have been developed as a promising treatment approach for cocaine dependence. However, the stimulant effects of DAT inhibitors have the potential to disrupt sleep patterns, and the influence of long-term treatment on dopamine neurochemistry is still unknown. Objectives The objectives of this study were to (1) explore the stimulant-related effects of chronic DAT inhibitor (RTI-336) treatment on motor activity and sleep-like measures in male rhesus monkeys (Macaca mulatta; n=4) and (2) to determine the effect of drug treatment on prolactin and cortisol levels. Methods The effects of chronic (21 day) administration of the selective DAT inhibitor RTI-336 (1mg/kg/day; i.m.) were evaluated on locomotor activity, inactivity, and hormone levels. Subjects were fitted with a collar-mounted activity monitor to evaluate their motor activity, with 4 days of baseline recording preceding 3 weeks of daily saline or RTI-336 injections. Blood samples were collected immediately prior to and following chronic treatment. Results RTI-336 produced a significant increase in locomotor activity at the end of the daytime period compared to saline administration. During the 3-week treatment period, sleep efficiency was decreased and the fragmentation index and latency to sleep onset were significantly increased. Hormone levels were not changed throughout the study. Conclusions Chronic treatment with RTI-336 has a mild but significant stimulant effect, as evidenced by the significant increase in activity during the evening period which may cause minor disruptions in sleep measures.