Dataset Information

Activation of Astrocytes in the Dorsomedial Striatum Facilitates Transition From Habitual to Goal-Directed Reward-Seeking Behavior.

ABSTRACT:

Background

Habitual reward-seeking behavior is a hallmark of addictive behavior. The role of the dorsomedial striatum (DMS) in regulating goal-directed reward-seeking behavior has been long appreciated. However, it remains unclear how the astrocytic activities in the DMS differentially affect the behavioral shift.

Methods

To investigate the astrocytic activity-driven neuronal synaptic events and behavioral consequences, we chemogenetically activated astrocytes in the DMS using GFAP promoter-driven expression of hM3Dq, the excitatory DREADDs (designer receptors exclusively activated by designer drugs). First, we confirmed the chemogenetically induced cellular activity in the DMS astrocytes using calcium imaging. Then, we recorded electrophysiological changes in the synaptic activity of the two types of medium spiny neurons (MSNs): direct and indirect pathway MSNs. To evaluate the behavioral consequences, we trained mice in nose-poking operant chambers that developed either habitual or goal-directed reward-seeking behaviors.

Results

The activation of DMS astrocytes reduced the frequency of spontaneous excitatory postsynaptic currents in the direct pathway MSNs, whereas it increased the amplitude of the spontaneous excitatory postsynaptic currents and decreased the frequency of spontaneous inhibitory postsynaptic currents in the indirect pathway MSNs. Interestingly, astrocyte-induced DMS neuronal activities are regulated by adenosine metabolism, receptor signaling, and transport. Importantly, mice lacking an astrocytic adenosine transporter, ENT1 (equilibrative nucleoside transporter 1; Slc29a1), show no transition from habitual to goal-directed reward-seeking behaviors upon astrocyte activation, while restoring ENT1 expression in the DMS facilitated this transition.

Conclusions

Our findings reveal that DMS astrocyte activation differentially regulates MSNs' activity and facilitates shifting from habitual to goal-directed reward-seeking behavior.

SUBMITTER: Kang S

PROVIDER: S-EPMC7584758 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionHarmful behavior such as smoking may reflect a disturbance in the balance of goal-directed and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ from controls (N = 46) in the regulation of goal-directed and habitual behavior. It was also investigated whether individual differences in nicotine dependence levels were associated with habitual responding.MethodsWe used two different multistage instrumental learning tasks that consist of an instrumental learning phase, subsequent outcome devaluation, and a testing phase to measure the balance between goal-directed and habitual responding. The testing phases of these tasks occurred after either appetitive versus avoidance instrumental learning. The appetitive versus aversive instrumental learning stages in the two different tasks modeled positive versus negative reinforcement, respectively.ResultsSmokers and nonsmoking controls did not differ on habitual versus goal-directed control in either task. Individual differences in nicotine dependence within the group of smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding.ConclusionsThe current finding highlights the importance of individual differences within smokers. For future research, neuroimaging studies are suggested to further unravel the nature of the imbalance between goal-directed versus habitual control in severely dependent smokers by directly measuring activity in the corresponding brain systems.ImplicationsGoal-directed versus habitual behavior in substance use and addiction is highly debated. This study investigated goal-directed versus habitual control in smokers. The findings suggest that smokers do not differ from controls in goal-directed versus habitual control. Individual differences in nicotine dependence within smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. These findings add to the ongoing debate on habitual versus goal-directed control in addiction and emphasize the importance of individual differences within smokers.

Project description:The opioid-receptor antagonist naltrexone (NTX) reduces goal-directed alcohol drinking in rats presumably by blunting alcohol reward. However, different operant conditioning behavior can be produced by different reinforcement schedules, with goal-directed operant behavior being more sensitive to changes in reward value than less flexible, habit-associated models. We tested the hypothesis that NTX more effectively reduces alcohol drinking and seeking in a goal-directed than in a habit-associated operant model, and more effectively reduces alcohol versus sucrose self-administration, consistent with diminished alcohol reward.Rats were trained to self-administer 10% alcohol or 1.5% sucrose in a lever-press task and then underwent a within-subject assessment of NTX (0.1 to 1 mg/kg) effects on operant behavior. A fixed-ratio (FR5) reinforcement schedule was used to model goal-directed behavior, and a variable-interval (VI30) schedule was used to model habitual behavior.As predicted, NTX reduced fluid deliveries earned by the FR5-alcohol group significantly more than all other groups. However, NTX reduced lever presses during self-administration sessions in VI30-trained rats without reducing earned deliveries, due to the low contingency between rate of pressing and fluid deliveries under that schedule. Interestingly, when fluid delivery was withheld (extinction), NTX reduced reward-seeking in all rats. Finally, NTX blocked reinstatement of reward-seeking upon presentation of 0.2 ml alcohol or sucrose and associated cues in the FR5-trained but not VI30-trained rats.NTX reduced goal-directed alcohol drinking compared with other operant conditions. In addition, NTX blocked reinstatement of reward-seeking in rats trained on the goal-directed FR5 reinforcement schedule but not in rats trained on the habit-like VI30 reinforcement schedule. However, NTX also exerted nonspecific effects on reward-seeking that were revealed under low-effort contingency conditions or absence of reward. Together, these data support the hypothesis that NTX is less effective in conditioning models that are more habit-associated.