Abstinence from cocaine self-administration promotes microglia pruning of astrocytes which drives cocaine-seeking behavior.

Rodent drug self-administration leads to compromised ability of astrocytes to maintain glutamate homeostasis within the brain's reward circuitry, as well as reductions in surface area, volume, and synaptic colocalization of astrocyte membranes. However, the mechanisms driving astrocyte responses to cocaine are unknown. Here, we report that long-access cocaine self-administration followed by prolonged home cage abstinence results in decreased branching complexity of nucleus accumbens astrocytes, characterized by the loss of peripheral processes.

Astrocyte-Neuron Interactions in Substance Use Disorders.

Engagement of astrocytes within the brain's reward circuitry has been apparent for approximately 30 years, when noncontingent drug administration was observed to lead to cytological markers of reactive astrocytes. Since that time, advanced approaches in rodent behavior and astrocyte monitoring have revealed complex interactions between astrocytes with drug type, animal sex, brain region, and dose and duration of drug administration. A number of studies now collectively reveal that rodent drug self-administration followed by prolonged abstinence results in decreased features of structure and synaptic colocalization of astrocytes.

Investigating cocaine- and abstinence-induced effects on astrocyte gene expression in the nucleus accumbens.

In recent years, astrocytes have been increasingly implicated in cellular mechanisms of substance use disorders (SUD). Astrocytes are structurally altered following exposure to drugs of abuse; specifically, astrocytes within the nucleus accumbens (NAc) exhibit significantly decreased surface area, volume, and synaptic colocalization after operant self-administration of cocaine and extinction or protracted abstinence (45 days). However, the mechanisms that elicit these morphological modifications are unknown.

Abstinence-Dependent Effects of Long-Access Cocaine Self-Administration on Nucleus Accumbens Astrocytes Are Observed in Male, But Not Female, Rats.

Accumulating evidence indicates significant consequences for astrocytes associated with drug abuse. For example, reductions in structural features and synaptic colocalization of male rat nucleus accumbens (NAc) astrocytes are observed following short-access (ShA; 2 h/d) self-administration and extinction from cocaine, methamphetamine, and heroin. However, it is unknown whether these observations extend to other rodent models of drug abuse, how enduring these effects may be, and whether similar effects are observed in female rats.

The synthetically produced predator odor 2,5-dihydro-2,4,5-trimethylthiazoline increases alcohol self-administration and alters basolateral amygdala response to alcohol in rats.

Post-traumatic stress disorder (PTSD) is a psychiatric illness that can increase the risk for developing an alcohol use disorder (AUD). While clinical data has been useful in identifying similarities in the neurobiological bases of these disorders, preclinical models are essential for understanding the mechanism(s) by which stressors increase the risk for escalated alcohol consumption. The purpose of these studies was to examine if exposure of male Long-Evans rats to the synthetically derived predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT; a component of fox feces) would increase sweetened alcohol self-administration, potentially by facilitating transfer of salience towards cues, and alter neuronal response to alcohol as measured by the immediate early gene c-Fos.