Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder.

In brain, the striatum is a heterogenous region involved in reward and goal-directed behaviors. Striatal dysfunction is linked to psychiatric disorders, including opioid use disorder (OUD). Striatal subregions are divided based on neuroanatomy, each with unique roles in OUD.

A Glitch in the Matrix: The Role of Extracellular Matrix Remodeling in Opioid Use Disorder.

Opioid use disorder (OUD) and deaths from drug overdoses have reached unprecedented levels. Given the enormous impact of the opioid crisis on public health, a more thorough, in-depth understanding of the consequences of opioids on the brain is required to develop novel interventions and pharmacological therapeutics. In the brain, the effects of opioids are far reaching, from genes to cells, synapses, circuits, and ultimately behavior.

Dorsal Raphe 5-HT Neurons Utilize, But Do Not Generate, Negative Aversive Prediction Errors.

The dorsal raphe nucleus (DRN) contains the largest population of serotonin (5-HT) neurons in the central nervous system. 5-HT, synthesized via tryptophan hydroxylase 2 (Tph2), is a widely functioning neuromodulator implicated in fear learning. Here, we sought to investigate whether DRN 5-HT is necessary to reduce fear via negative prediction error (-PE).

Threat and Bidirectional Valence Signaling in the Nucleus Accumbens Core.

Appropriate responding to threat and reward is essential to survival. The nucleus accumbens core (NAcc) is known to support and organize reward behavior. The NAcc is also necessary to fully discriminate threat and safety cues.

Ventral pallidum neurons dynamically signal relative threat.

The ventral pallidum (VP) is anatomically poised to contribute to threat behavior. Recent studies report a VP population that scales firing increases to reward but decreases firing to aversive cues. Here, we tested whether firing decreases in VP neurons serve as a neural signal for relative threat.

The Nucleus Accumbens Core is Necessary to Scale Fear to Degree of Threat.

Fear is adaptive when the level of the response rapidly scales to degree of threat. Using a discrimination procedure consisting of danger, uncertainty, and safety cues, we have found rapid fear scaling (within 2 s of cue presentation) in male rats. Here, we examined a possible role for the nucleus accumbens core (NAcc) in the acquisition and expression of fear scaling.

Operant over-responding is more sensitive than reversal learning for revealing behavioral changes after withdrawal from alcohol consumption.

In humans, prior alcohol use is linked with impulsivity and impaired decision-making, but the nature of this relationship is unclear. In a previous study in rats, we found that prior alcohol access led to over-responding in go/no-go discrimination training, but had no effect on discrimination learning. It was unclear whether this over-responding effect would occur in a reversal learning task, or whether prior alcohol would impair reversal learning in our task.

Lateral orbitofrontal cortex partitions mechanisms for fear regulation and alcohol consumption.

Anxiety disorders and alcohol use disorder are highly comorbid, yet identifying neural dysfunction driving comorbidity has been challenging. Lateral orbitofrontal cortex (lOFC) dysfunction has been independently observed in each disorder. Here we tested the hypothesis that the lOFC is essential to partition mechanisms for fear regulation and alcohol consumption.

Early adolescent adversity inflates threat estimation in females and promotes alcohol use initiation in both sexes.

Childhood adversity is associated with exaggerated threat processing and earlier alcohol use initiation. Conclusive links remain elusive, as childhood adversity typically co-occurs with detrimental socioeconomic factors, and its impact is likely moderated by biological sex. To unravel the complex relationships among childhood adversity, sex, threat estimation, and alcohol use initiation, we exposed female and male Long-Evans rats to early adolescent adversity (EAA).

Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders.

Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood.

Prior alcohol consumption does not impair go/no-go discrimination learning, but causes over-responding on go trials, in rats.

Prior alcohol use is associated with impaired response inhibition in humans, including in laboratory go/no-go discrimination tasks. In two experiments, we determined whether chronic intermittent access to alcohol would alter go/no-go discrimination learning. Rats received 4-6 weeks of chronic intermittent access to 20% alcohol (alone or accompanied by saline or 1.