Dextromethorphan reduces sign-tracking but not goal-tracking in male Sprague-Dawley rats.

Sign-tracking is a well-known phenomenon in appetitive Pavlovian conditioning in which subjects approach the site of a conditioned stimulus (CS) associated with an appetitive unconditioned stimulus (US) even when the two are located separately. Control of sign-tracking may be important in rehabilitation from drug dependence to help ward off relapse. Recent studies have found success in using ketamine to reduce sign-tracking. In this study, we employed a similar but unscheduled drug, dextromethorphan (DXM), which affects many of the same molecular targets as ketamine, in an attempt to reduce sign-tracking in a standard paradigm. DXM was found to reduce sign-tracking at the doses examined in this study, while goal-tracking (approaching the site of the US rather than CS) was relatively unaffected. DXM offers advantages over ketamine in terms of use with patients and may have some utility in rehabilitation.

Acute MK-801 increases measures of both sign-tracking and goal-tracking in male Sprague-Dawley rats.

Sign-tracking is a Pavlovian conditioned approach behavior thought to be important in understanding cue-driven relapse to drug use, and strategies for reducing sign-tracking may have some benefit in preventing relapse. A previous study successfully employed the NMDA receptor antagonist MK-801 in preventing the development of sign-tracking (but not goal-tracking) in a conditioned approach task. In this study, we focused on whether MK-801 would have similar effects on previously established sign-tracking behavior. MK-801 was administered after training in a standard sign-/goal-tracking task using a retractable lever as a conditioned stimulus and a sucrose pellet as unconditioned stimulus. It was found that MK-801 increased measures of both sign- and goal-tracking in subjects who had previously learned the task. The NMDA receptor appears to play a complex role in governing behavior related to sign-tracking.

Effects of bupropion on sign- and goal-tracking in male Sprague Dawley rats.

Relapse into addiction is often triggered by cues that have a Pavlovian association with drugs and drug-taking. Sign-tracking involves approach of and interaction with Pavlovian conditioned signals for appetitive events (as opposed to goal-tracking, which involves approach of the site of the appetitive events themselves) and may be important in understanding cue-driven relapse. Bupropion is an atypical antidepressant and smoking cessation aid with effects on dopamine and norepinephrine that may have some utility in reducing sign-tracking. Male Sprague-Dawley rats were trained in a task where sign- and goal-tracking were possible and then administered doses of bupropion during a test phase. Bupropion decreased measures of sign-tracking and increased goal-tracking. This suggests that bupropion might be a useful adjunct medication for many kinds of behavioral disorders in which cue-driven behavior is problematic.

Effects of two kinds of noradrenergic ADHD medicines on sign-tracking and goal-tracking in male rats.

Sign- and goal-tracking are behaviors seen in many species when a conditioned stimulus and it's corresponding unconditioned stimulus are presented at separate locations, and have been the focus of studies on appetitive conditioned and drug dependence. The neurochemical basis of sign-tracking is of interest for both studies of basic conditioning and addiction. In this work, I examined the role of norepinephrine by employing two noradrenergic drugs used for attention-deficit hyperactivity disorder (ADHD)-(a) atomoxetine, a norepinephrine reuptake blocker, and (b) guanfacine, an α2A-adrenergic receptor agonist. Sprague-Dawley rats were trained using a standard Pavlovian conditioning procedure with a retractable lever as conditioned stimulus and sucrose pellets as unconditioned stimulus. It was found that while atomoxetine reduced both sign- (both doses) and goal-tracking (only at the higher dose), guanfacine did not have any effect on either behavior. While norepinephrine reuptake blocking may be an effective strategy for reducing sign-tracking, manipulation of the α2A-adrenergic receptor appears less viable. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Lipopolysaccharide-induced immune activation impairs attention but has little effect on short-term working memory.

Cytokine-induced CNS inflammation has been theorized to contribute to cognitive dysfunction in sickness and neurodegenerative disease. We investigated the effects of systemic endotoxin-induced acute immune activation and inflammation on working memory and attention functions in pigeons assessed through two variations of an operant symbolic matching-to-sample (SMTS) task, employing doses of lipopolysaccharide (LPS) sufficient to induce fever. LPS produced moderate impairments in comparison to saline on the SMTS task designed to measure visual vigilance and attention, but the impairments were not as marked as those produced by chlordiazepoxide (CDP) which is known to disrupt attention. In contrast, LPS had no significant effect on short-term working memory performance compared to saline, while scopolamine, a cholinergic antagonist known to disrupt working memory, did impair performance. The results have implications for the cognitive impairments seen in illnesses characterized by chronic cytokine activation (e.g., Alzheimer's disease) as well as illnesses treated with cytokines (e.g., multiple sclerosis) suggesting that some cognitive failures attributed to working memory impairments per se may better be attributed to prior attention impairments.

Behavioral effects of mefloquine in tail suspension and light/dark tests.

Mefloquine hydrochloride has been used widely in the past few decades for malaria prophylaxis and treatment. However, in recent years, it has fallen out of favor due to reports of exposure being linked to numerous neuropsychiatric effects, including emotional disturbances. In this study we examined the effects of different doses (5, 25, or 100 mg/kg) of mefloquine relative to vehicle on male C57BL/6 J mice in two tests of emotional behavior, the light-dark box and the tail suspension test. It was found that mefloquine exposure reduced anxiety-linked behaviors in the light-dark box and reduced total immobility times in the tail suspension test, especially at higher doses. Our results lend support to the notion that mefloquine exposure could induce emotional disinhibition.

Effects of lipopolysaccharide on consolidation of partial learning in the Y-maze.

Research on consolidation of long-term memory suggests that acute immune system activation induced by endotoxin lipopolysaccharide (LPS) may disrupt consolidation of newly acquired learning. Adult male Sprague-Dawley rats were trained to perform a simple Y-maze task and were immediately afterwards administered LPS (15 microg/kg) or saline. After a seven-day interval, subjects were returned to the Y-maze and were retrained to criterion. It was found that subjects treated with saline required significantly fewer trials to relearn the task relative to the LPS group and a no-partial-learning control group, which themselves did not differ. These results are most readily explained in terms of a disruptive effect of acute immune system activation on consolidation of newly induced acquired memories.

Effects of acute amphetamine exposure on two kinds of Pavlovian approach behavior.

Two kinds of Pavlovian conditioned approach behavior are possible: approach of the CS (sign-tracking) and approach of the US (goal-tracking). We hypothesized that administration of AMP would increase sign-tracking and decrease goal-tracking. However, increasing doses of AMP (up to 2.0mg/kg) decreased measures of sign-tracking while simultaneously increasing measures of goal-tracking. Administration of AMP may shift responding from cues distant from the CS to cues closer to the CS.