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

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.

Dose-dependent differences in short ultrasonic vocalizations emitted by rats during cocaine self-administration.

RATIONALE: The motivational impetuses underlying self-administration of cocaine and other drugs of abuse are not fully understood. One emerging factor is affect. Both positive and negative affective states have been hypothesized to influence drug seeking and drug taking. In parallel, it has been posited that the ultrasonic vocalizations (USVs) of Rattus norvegicus provide insight into the animals' affective reactions. Furthermore, it has been shown that mesolimbic dopamine (DA) plays a key role in cocaine self-administration and in USV production. Thus, affective processing as measured by rodent USVs likely coincides with cocaine self-administration, but to date has not been studied. OBJECTIVE: The present study examined USVs in both the negative affective (18-32.99 kHz) and positive affective (38-80 kHz) ranges of rats during self-administration of a low (0.355 mg/kg/infusion) or high (0.71 mg/kg/infusion) dose of cocaine. RESULTS: USVs in both ranges were observed in both dose groups. Vocalizations of the low-dose animals occurred primarily in the 22-kHz range (18-32.99 kHz), but exhibited shorter durations (10-500 ms) than those traditionally observed for 22-kHz calls in aversive situations. In contrast, USVs of the high-dose group were primarily observed in the 50-kHz frequency range (38-80 kHz), typically associated with appetitive outcomes. CONCLUSIONS: These results provide evidence for the presence of USVs during cocaine self-administration. The observed dose-dependent difference in USVs provides novel support for the view that affect is one potential motivational factor influencing human drug use and relapse behaviors. Rodent USVs may provide a powerful tool for understanding the role of affect in addiction.