Differential roles of ventral pallidum subregions during cocaine self-administration behaviors

• Published in: Journal of comparative neurology (1911) Vol. 521; no. 3; pp. 558 - 588
• Main Authors: Root, David H., Ma, Sisi, Barker, David J., Megehee, Laura, Striano, Brendan M., Ralston, Carla M., Fabbricatore, Anthony T., West, Mark O.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.02.2013; Wiley Subscription Services, Inc
• Subjects: accumbens; Action Potentials - drug effects; Action Potentials - physiology; Animals; Behavior, Animal - physiology; Calbindins; Cocaine - pharmacology; Cocaine-Related Disorders - physiopathology; Conditioning, Operant - physiology; Cues; dopamine; Dopamine Uptake Inhibitors - pharmacology; Drug-Seeking Behavior - physiology; Globus Pallidus - cytology; Globus Pallidus - drug effects; Globus Pallidus - physiology; Head Movements - physiology; Male; Neurons - drug effects; Neurons - physiology; Neurotensin - metabolism; Nucleus Accumbens - cytology; Nucleus Accumbens - drug effects; Nucleus Accumbens - physiology; pallidum; Rats; Rats, Long-Evans; S100 Calcium Binding Protein G - metabolism; Self Administration; striatopallidum; striatum; Substance P - metabolism; Subthalamic Nucleus - cytology; Subthalamic Nucleus - drug effects; Subthalamic Nucleus - physiology
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.23191

The ventral pallidum (VP) is necessary for drug‐seeking behavior. VP contains ventromedial (VPvm) and dorsolateral (VPdl) subregions, which receive projections from the nucleus accumbens shell and core, respectively. To date no study has investigated the behavioral functions of the VPdl and VPvm subregions. To address this issue, we investigated whether changes in firing rate (FR) differed between VP subregions during four events: approaching toward, responding on, or retreating away from a cocaine‐reinforced operandum and a cocaine‐associated cue. Baseline FR and waveform characteristics did not differ between subregions. VPdl neurons exhibited a greater change in FR compared with VPvm neurons during approaches toward, as well as responses on, the cocaine‐reinforced operandum. VPdl neurons were more likely to exhibit a similar change in FR (direction and magnitude) during approach and response than VPvm neurons. In contrast, VPvm firing patterns were heterogeneous, changing FRs during approach or response alone, or both. VP neurons did not discriminate cued behaviors from uncued behaviors. No differences were found between subregions during the retreat, and no VP neurons exhibited patterned changes in FR in response to the cocaine‐associated cue. The stronger, sustained FR changes of VPdl neurons during approach and response may implicate VPdl in the processing of drug‐seeking and drug‐taking behavior via projections to subthalamic nucleus and substantia nigra pars reticulata. In contrast, the heterogeneous firing patterns of VPvm neurons may implicate VPvm in facilitating mesocortical structures with information related to the sequence of behaviors predicting cocaine self‐infusions via projections to mediodorsal thalamus and ventral tegmental area. J. Comp. Neurol. 521:558–588, 2013. © 2012 Wiley Periodicals, Inc. Dorsolateral ventral pallidum (VPdl) neurons exhibit greater changes in firing rate (FR) during cocaine‐seeking responses than ventromedial ventral pallidum (VPvm) neurons. y Axis is cumulative proportion of neurons; x axis is absolute change in FR during response. Red and black lines indicate cumulative proportions for VPdl and VPvm neurons, respectively. Median values are circle (VPdl) and square (VPvm). Accumbens shell and core project to VPvm and VPdl, respectively, suggesting that the core‐VPdl subcircuit is especially critical for drug‐seeking behavior. **P < 0.01.