Extracellular Dopamine Levels in Nucleus Accumbens after Chronic Stress in Rats with Persistently High vs. Low 50-kHz Ultrasonic Vocalization Response

Abstract

Fifty-kHz ultrasonic vocalizations (USVs) in response to an imitation of rough-and-tumble play ('tickling') have been associated with positive affective states and rewarding experience in the rat. This USV response can be used as a measure of inter-individual differences in positive affect. We have previously shown that rats with persistently low positive affectivity are more vulnerable to the effects of chronic variable stress (CVS). To examine whether these differential responses are associated with dopaminergic neurotransmission in the nucleus accumbens (NAc), juvenile male Wistar rats were categorized as of high or low positive affectivity (HC and LC, respectively), and after reaching adulthood, extracellular dopamine (DA) levels in the NAc shell were measured using in vivo microdialysis after three weeks of CVS. Baseline levels of DA were compared as well as the response to K⁺-induced depolarization and the effect of glial glutamate transporter EAAT2 inhibition by 4 mM l-trans-pyrrolidine-2,4-dicarboxylate (PDC). DA baseline levels were higher in control LC-rats, and stress significantly lowered the DA content in LC-rats. An interaction of stress and affectivity appeared in response to depolarization where stress increased the DA output in HC-rats whereas it decreased it in LC-rats. These results show that NAc-shell DA is differentially regulated in response to stress in animals with high and low positive affect.

Keywords: 50-khz ultrasonic vocalizations (USVs); chronic variable stress (CVS); dopamine; individual differences; microdialysis; nucleus accumbens.

Figure 1

The general timeline of experimental procedures. DA, dopamine; MD, microdialysis; NAc, nucleus accumbens; PND, postnatal day; USVs, ultrasonic vocalizations.

Figure 2

Cumulative weight gain in the middle (day 11 of stress) and after the three-week stress regimen (average ± SEM). #, ## p < 0.05, 0.01 vs. LC-control; and p < 0.05 vs. HC-control. HC-controls: n = 8; HC-stress, n = 8; LC-controls, n = 7; and LC-stress, n = 6. HC, high 50-kHz USV rats, LC, low 50-kHz USV rats.

Figure 3

Extracellular dopamine levels in the NAc shell as measured during microdialysis (average + or-SEM). Baseline (samples 2–4), perfusion with 50 mM KCl solution (samples 5–7), and perfusion with 4 mM l-trans-pyrrolidine-2,4-dicarboxylate (PDC) (samples 13–15). HC-controls, n = 8; HC-stress, n = 8; LC-controls, n = 7; and LC-stress, n = 6. HC, high 50-kHz USV rats and LC, low 50-kHz USV rats.

Figure 4

Extracellular dopamine levels in the NAc shell as measured during microdialysis (average ± SEM). (A) Average in baseline dopamine content (samples 2–4), (B) area under the curve (AUC) during and after perfusion with 50 mM KCl solution (samples 5–11), (C) area under the curve (AUC) during and after perfusion with 4 mM PDC (samples 13–20). ## p < 0.01 vs. LC-control; and p < 0.05 vs. HC-control. HC-controls, n = 8; HC-stress, n = 8; LC-controls, n = 7; and LC-stress: n = 6. HC, high 50-kHz USV rats and LC, low 50-kHz USV rats.