Amphetamine Modulation of Long-Term Object Recognition Memory in Rats: Influence of Stress

Abstract

Amphetamine is a potent psychostimulant that increases brain monoamine levels. Extensive evidence demonstrated that norepinephrine is crucially involved in the regulation of memory consolidation for stressful experiences. Here, we investigated amphetamine effects on the consolidation of long-term recognition memory in rats exposed to different intensities of forced swim stress immediately after training. Furthermore, we evaluated whether such effects are dependent on the activation of the peripheral adrenergic system. To this aim, male adult Sprague Dawley rats were subjected to an object recognition task and intraperitoneally administered soon after training with amphetamine (0.5 or 1 mg/kg), or its corresponding vehicle. Rats were thereafter exposed to a mild (1 min, 25 ± 1°C) or strong (5 min, 19 ± 1°C) forced swim stress procedure. Recognition memory retention was assessed 24-h after training. Our findings showed that amphetamine enhances the consolidation of memory in rats subjected to mild stress condition, while it impairs long-term memory performance in rats exposed to strong stress. These dichotomic effects is dependent on stress-induced activation of the peripheral adrenergic response.

Keywords: adrenal medullectomy; forced swim stress; memory consolidation; norepinephrine; posttraumatic stress disorder.

FIGURE 1

Amphetamine effects on the consolidation of long-term OR memory in rats exposed to the mild stress condition immediately after training. DI on the testing trial for vehicle- and amphetamine-treated rats that were subjected to the mild stress condition immediately after training. Post hoc comparisons reported significant differences between groups as follows: *p < 0.05 vs the corresponding vehicle group. ##p < 0.01, one-sample t-test significantly different from zero. Data are expressed as mean ± SEM (n = 8–9 per group).

FIGURE 2

Amphetamine effects on the consolidation of long term OR memory in rats exposed to the strong stress condition immediately after training. DI on the testing trial for vehicle- and amphetamine-treated rats that were subjected to the strong stress condition immediately after training. Post hoc comparisons reported significant differences between groups as follows: *p < 0.05 vs the corresponding vehicle group. #p < 0.05, one-sample t-test significantly different from zero. Data are expressed as mean ± SEM (n = 10–11 per group).

FIGURE 3

Influence of the peripheral adrenergic system on amphetamine effects on the long-term OR memory consolidation in rats exposed to the mild stress condition immediately after training. DI on the testing trial for sham and medullectomized rats that were treated with vehicle or amphetamine and subjected to the mild stress condition immediately after training. Post hoc comparisons reported significant differences between groups as follows: **p < 0.01 vs the corresponding vehicle group. °p < 0.01 vs. the corresponding sham group. ###p < 0.001, one-sample t-test significantly different from zero. Data are expressed as mean ± SEM (n = 8–13 per group).

FIGURE 4

Influence of the peripheral adrenergic system on amphetamine effects on the long-term OR memory consolidation in rats exposed to the strong stress condition immediately after training. DI on the testing trial for sham and medullectomized rats that were treated with vehicle or amphetamine and subjected to the strong stress condition immediately after training. Post hoc comparisons reported significant differences between groups as follows: °p < 0.05; °p < 0.01 vs the corresponding sham group. #p < 0.05; ###p < 0.001, one-sample t-test significantly different from zero. Data are expressed as mean ± SEM (n = 10–12 per group).