Traumatic experiences can leave lasting memories that affect how people respond to stress, danger, and reminders of the past. For individuals living with post-traumatic stress disorder (PTSD), these responses may occur alongside substance use problems. 

PTSD and substance use disorders frequently co-occur, and people experiencing both conditions often face greater challenges in treatment and a higher likelihood of returning to substance use. Yet, researchers are still working to understand how persistent fear memories may influence drug use and drug-seeking behavior in the brain. 

A new preclinical study from researchers at the Rutgers Addiction Research Center in the Brain Health Institute and the Rutgers Robert Wood Johnson Medical School Department of Psychiatry offers new insight into this relationship. Published in Neuropharmacology, the study examined whether an established fear memory could later affect cocaine use and cocaine-seeking behavior in male and female rats.  

Studying the Connection Between Fear and Cocaine Use 

Fear learning is an important survival mechanism. When an experience signals danger, the brain learns to associate certain sounds, places, or other cues with that threat. Later exposure to the same cue can trigger a fear response, even when the original danger is no longer present. This process can become harmful when fear memories remain unusually strong or are activated in situations that are no longer dangerous, as persistent responses to trauma-related reminders are a central feature of PTSD. 

To study how these memories might interact with substance use, the Rutgers researchers combined a rat model of PTSD known as fear conditioning with cocaine self-administration. 

During fear conditioning, rats heard an audio tone that was paired with a mild footshock. The researchers later played the tone again without the footshock. Both male and female rats that had undergone fear conditioning showed a fear response that persisted for weeks, indicating that they remembered the association between the tone and the threatening experience. After fear conditioning, the rats were given the opportunity to self-administer cocaine, which was given intravenously when a lever was pressed.  

Fear Conditioning Increased Cocaine-Related Behaviors in Male but not Female Rats 

The researchers found that prior fear conditioning increased subsequent cocaine intake only in male rats. Male rats that had learned to associate the tone with the footshock pressed the lever for cocaine more frequently than males in the control group.  

These results highlight the lasting effects of cued fear memories, which enhanced subsequent cocaine-reinforced behaviors only in male rats. These findings have important implications for clinical interactions between PTSD and substance use disorders. 

The reasons for the profound sex differences are not yet clear. The researchers note that stress hormones, ovarian hormones, and different phases of the reproductive cycle could potentially influence the interaction between fear and cocaine. Additional research will be needed to understand the biological mechanisms behind the sex-specific findings. 

What Was Happening in the Brain? 

The researchers also examined activity within the basolateral amygdala (BLA). The amygdala is often associated with fear, but its role is broader. It helps the brain evaluate the emotional importance of experiences and form memories related to both threats and rewards. The researchers found that fear conditioning increased the excitability of BLA neurons, which may represent a neuronal conduit through which traumatic emotional memories enhance subsequent responses to drugs of abuse such as cocaine. 

Why These Findings Matter 

PTSD and substance use disorders are complex conditions shaped by many biological, psychological, social, and environmental factors. Understanding why they frequently occur together may help researchers identify more effective approaches to prevention and treatment. 

This study provides a new model for examining how persistent fear memories may affect later cocaine use and responsiveness to drug-associated cues. It also highlights the importance of studying males and females separately rather than assuming that the same biological processes operate identically across sexes. 

Important Limitations 

Because this research was conducted in rats, the findings should be viewed as an early step toward understanding how fear memories and cocaine-related behaviors may interact. Fear conditioning allows researchers to study specific aspects of learning and memory, but it cannot capture the full complexity of human trauma or PTSD. 

The study also focused only on cocaine, so future research will need to examine whether similar patterns emerge with other drugs of abuse and how hormones, stress-response systems, and additional brain regions may contribute. 

Building a Clearer Picture of PTSD and Substance Use 

Fear and reward memories can both have a powerful influence on behavior. By investigating how these systems interact, researchers can begin to identify the brain processes that may contribute to co-occurring PTSD and substance use disorders. 

The Rutgers study suggests that learned fear, rather than exposure to stress alone, may influence later cocaine-related behavior through lasting changes in brain circuits involved in emotional and reward-related memories. It also shows that these effects may differ by sex, providing another step toward understanding the complex biological relationship between trauma, memory, and addiction. 

Date: August 7, 2026
By: Ricki Arvesen