Memantine decreases measures of sign-tracking and increases measures of goal-tracking in male Sprague Dawley rats

Abstract

Memantine is a drug which has antagonistic effects at N-methyl-D-aspartate and 5-hydroxytryptamine3 receptors. Its properties may make it especially effective at reducing sign-tracking, a Pavlovian conditioned approach behavior of a conditioned stimulus, which is implicated in relapse to use of addictive drugs, and thereby provide support to patients who attempting to overcome relapse and addiction. Male Sprague-Dawley rats were trained in a Pavlovian conditioning task using a retractable lever as a conditioned stimulus and sucrose pellets as unconditioned stimuli, which can elicit either sign-tracking or goal-tracking (approach of the site of unconditioned stimulus delivery). Subjects in this task are classified in three behavioral phenotypes – sign-tracker, goal-tracker, or intermediate – depending on levels of sign- and goal-tracking shown at the end of training. Afterward drug testing began and the effects of two doses of memantine were compared with vehicle. It was found that memantine acutely reduced measures of sign-tracking and increased goal-tracking measures, depending on behavioral phenotype, with sign-trackers and intermediates showing the strongest effects. The results of this study suggest that memantine may have use in reducing the incentive salience of reward-related cues.