Neurons of the Ventral Tegmental Area Encode Individual Differences in Motivational "Wanting" for Reward Cues.

It has been argued that the dopaminergic system is involved in the attribution of motivational value to reward predictive cues as well as prediction error. To evaluate, dopamine neurons were recorded from male rats performing a Pavlovian approach task containing cues that have both "predictive" and "incentive" properties. All animals learned the predictive nature of the cue (illuminated lever entry into cage), but some also found the cue to be attractive and were motivated toward it ("sign-trackers," STs). "Goal-trackers" (GTs) predominantly approached the location of reward receptacle. Rats were implanted with tetrodes for neural electrophysiological recordings in the ventral tegmental area. Cells were characterized by spike waveform shape and firing rate. Firing rates and magnitudes of responses in relation to Pavlovian behaviors, cue presentation, and reward delivery were assessed. We identified 103 dopamine and 141 nondopamine neurons. GTs and STs both showed responses to the initial lever presentation (CS1) and lever retraction (CS2). However, higher firing rates were sustained during the lever interaction period only in STs. Further, dopamine cells of STs showed a significantly higher proportion of cells responding to both CS1 and CS2. These are the first results to show that neurons from the VTA encode both predictive and incentive cues, support an important role for dopamine neurons in the attribution of incentive salience to reward-paired cues, and underscore the consequences of potential differences in motivational behavior between individuals.SIGNIFICANCE STATEMENT This project serves to determine whether dopamine neurons encode differences in cued approach behaviors and incentive salience. How neurons of the VTA affect signaling through the NAcc and subsequent dopamine release is still not well known. All cues that precede a reward are predictive in nature. Some, however, also have incentive value, in that they elicit approach toward them. We quantified the attribution of incentive salience through cue approach behavior and cue interaction, and the corresponding magnitude of VTA neural firing. We found dopamine neurons of the VTA encode strength of incentive salience of reward cues. This suggests that dopamine neurons specifically in the VTA encode motivation.

Cocaine-induced plasticity, motivation, and cue responsivity do not differ in obesity-prone vs obesity-resistant rats; implications for food addiction.

RATIONALE: Compared to obesity-resistant rats, obesity-prone rats consume more food, work harder to obtain food, show greater motivational responses to food-cues, and show greater striatal plasticity in response to eating sugary/fatty foods. Therefore, it is possible that obesity-prone rats may also be more sensitive to the motivational properties of cocaine and cocaine-paired cues, and to plasticity induced by cocaine. OBJECTIVE: To examine baseline differences in motivation for cocaine and effects of intermittent access (IntA) cocaine self-administration on cocaine motivation, neurobehavioral responsivity to cocaine-paired cues, and locomotor sensitization in male obesity-prone vs obesity-resistant rats. METHODS: Intravenous cocaine self-administration was used to examine drug-taking and drug-seeking in males. Motivation for cocaine was measured using a within session threshold procedure. Cue-induced c-Fos expression in mesocorticolimbic regions was measured. RESULTS: Drug-taking and drug-seeking, cue-induced c-Fos, locomotor sensitization, and preferred level of cocaine consumption (Q0) were similar between obesity-prone and obesity-resistant groups. Maximal responding during demand testing (Rmax) was lower in obesity-prone rats. IntA experience enhanced motivation for cocaine (Pmax) in obesity-prone rats. CONCLUSIONS: The results do not support robust inherent differences in motivation for cocaine, cue-induced cocaine seeking, or neurobehavioral plasticity induced by IntA in obesity-prone vs obesity-resistant rats. This contrasts with previously established differences seen for food and food cues in these populations and shows that inherent enhancements in motivation for food and food-paired cues do not necessarily transfer to drugs and drug-paired cues.