Recruitment of Neuronal Populations in the Paraventricular Thalamus of Alcohol-Seeking Rats With Withdrawal-Related Learning Experience

Background

Stimulus-reactive neuronal populations are groups of neurons that become activated by environmental stimuli. These sparsely activated neuronal assemblies are implicated in encoding associations between environmental contexts and subjectively rewarding or aversive experiences that regulate behavior. How positive or negative hedonic states are represented in brain neurocircuits is a fundamental question relevant for understanding the processing of emotionally meaningful stimuli that drive appropriate versus maladaptive behavior. It is well known that animals avoid noxious stimuli and experiences. However, little is known about how the conditioning of environmental stimuli to behavior that leads to amelioration of dysphoric states establishes powerful associations that lead to compulsive maladaptive behavior.

Methods

Here, we sought to identify stimulus-reactive neurons that may mediate the conditioned effects of environmental stimuli associated with the reversal of dysphoric alcohol withdrawal states using a dependent withdrawal-related learning (WDL) experimental condition (DEP-WDL) (N = 13) and 3 controls: nondependent WDL (NDEP-WDL) (N = 12), dependent no-WDL (DEP-NWDL) (N = 9), NDEP-NWDL (N = 9).

Results

The results document a role for clusters of neurons in the paraventricular nucleus of the thalamus (N = 8), the central nucleus of the amygdala (N = 8), and the dorsal striatum (N = 9) in this conditioned negative reinforcement process.

Conclusions

These findings suggest that associations between reversal of negative hedonic states and environmental contexts are encoded in distinct neuronal populations that may serve as a neural substrate of compulsive alcohol seeking and vulnerability to relapse associated with reward dysregulation and hedonic allostasis.