Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats

Abstract

While reward-dependent facilitation of phasic dopamine signaling is well documented at both the cell bodies and terminals, little is known regarding fast dopamine transmission under aversive conditions. Exposure to aggressive confrontation is extremely aversive and stressful for many species including rats. The present study used fast-scan cyclic voltammetry and multiunit recording to determine if aggressive encounters and subsequent social defeat affect burst firing of ventral tegmental area (VTA) dopamine neurons and accumbal dopamine transients in defeated rats. Significant increases in the frequency of transient dopamine release were observed during interactions with an aggressive rat but not with a familiar cage mate. In agreement with voltammetric results, significant increases in burst frequency were detected in the VTA dopamine firing patterns during an aggressive confrontation; however, the number of spikes per burst remained unchanged. We found that neurons with lower burst rates under home cage conditions did not switch from nonbursting to bursting types, while neurons with higher burst levels showed amplified increases in bursting. This study demonstrates for the first time that aggressive confrontations in defeated rats are associated with increases in phasic dopamine transmission in the mesolimbic pathway.

Figure 1

The oxidative (+0.6 V) and reductive (−0.2 V) peaks (upper panel) of the dopamine transient (solid line) are compared with those of dopamine observed during electrical stimulation of dopamine fibers (dotted line) (A). The correlation of cyclic voltammograms from electrically evoked (lower panel, right) and transient (lower panel, left) dopamine verifies that the changes in electrochemical signal during the transient (lower panel, left) are attributable to the oxidation of dopamine. Representative traces of spontaneous dopamine transients in the nucleus accumbens of freely moving rats before and during presentation of cage mate (B) and aggressive resident (C). Cyclic voltammograms at the time of dopamine transients, which are indicated by asterisk, correlate with cyclic voltammograms at the time of electrically stimulated dopamine release (r² ≥ 0.75).

Figure 2

The effect of defeat stress on the frequency of dopamine transients in the nucleus accumbens of intruder rats. When the intruder rat is introduced to an aggressive resident environment, significant increases in dopamine transient activity are found during Confrontation and Post-confrontation periods. Data shown are mean ± SEM. ^*P<0.05.

Figure 3

Separation of neuronal populations and responses during aggression and social defeat. As has been demonstrated in previous strudies, putative dopamine and GABA neurons recorded with stainless steel multielectrode arrays can be identified by waveform duration and firing rates (A). There was no significant difference in dopamine firing rate during any condition. However, significant increases in burst firing were detected (B). These changes were due to increases in burst frequency (burst/min) but not spikes per burst (C). ^*P<0.05.

Figure 4

Responses of dopaminergic burst subtypes to aggressive confrontation. Representative interspike interval histograms demonstrate differences in burst profiles between GABA (left column) and dopamine neurons (right column) and between bursting and non-bursting dopamine neurons (A). Scatter plot shows that putative dopamine neurons with higher burst indices under homecage conditions show greater increases in bursting during confrontation with aggressive resident (B). First set of bars represents average ± SEM firing rates for bursting and non-bursting dopamine neurons. ANOVA analysis revealed significant effect of type only (C). Second set of bars represents average ± SEM burst firing levels in putative bursting and non-bursting dopamine neurons. There was a significant interaction between neuron type and condition.