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 homecage conditions did not switch from non-bursting 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.
In anesthetized animals, dopamine neurons fire in tonic and phasic firing modes hypothesized to be regulated by dissociable circuit mechanisms. Salient events critical to learning, reward processing, and attentional selection elicit transient phasic bursts. It is unclear, however, how burst activity contributes to sustained firing patterns in awake animals and if behavioral conditions known to affect dopaminergic neurotransmission change impulse activity levels. Acute stress is known to increase extracellular dopamine in the striatum and the prefrontal cortex. In this study, we have used multiunit recording to define and follow activity patterns in single dopaminergic neurons across days and to determine how restraint, a model of acute stress, changes tonic and phasic firing patterns. Long-term recording shows that a population of 23 putative dopamine neurons has heterogeneous firing profiles under baseline conditions. In all, 62% showed significant burst activity under resting conditions, while others showed predominantly regular (17%) or random (21%) activity patterns. Restraint increased mean firing rate in all dopamine neurons, but preferentially increased burst firing in neurons with higher burst rates under resting conditions. Finally, we show that increased burst firing can persist 24 h after a single exposure to stress. These data indicate that subsets of dopamine neurons may be sensitive to circuit mechanisms activated by stress and that persistent changes in burst firing may be evidence of synaptic plasticity. Furthermore, increased burst firing may be a mechanism through which stress augments extracellular dopamine in selected terminal regions.
Systemic baclofen administration attenuates responding for alcohol and sucrose reinforcement in a dose-dependent manner. If the reinforcing efficacy and response requirement for sucrose and alcohol are matched, then baclofen has similar effects on responding and patterns of drinking microstructure. We conclude that the neural mechanisms that support both ethanol and sucrose self-administration behavior are sensitive to gamma-aminobutyric acid type B modulation.
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