Diazepam selectively biases approach during threat-reward conflict while sparing reactive avoidance

Benzodiazepines are widely used to treat anxiety; however, their influence on defensive behavior when threats compete with rewards remains unclear.

Here, we tested the effects of diazepam on reactive avoidance (no conflict), threat-reward conflict resolution, and re-expression of avoidance following conflict.

Using an integrated platform-mediated avoidance paradigm in female and male rats, we assessed the effects of a low dose systemically administered diazepam (1 mg/kg).

Diazepam did not alter the reactive avoidance memory expression when threat cues were presented without a concurrent reward cue. In contrast, during the cued threat-reward conflict, diazepam reduced platform avoidance and increased reward engagement, shifting the avoidance/approach balance toward the approach. Diazepam also impaired the re-expression of avoidance following conflict training, maintaining a more approach-dominant behavioral allocation. Sex differences emerged selectively during post-conflict re-expression of avoidance, where diazepam produced a clearer shift toward reward engagement in males, whereas the effect in females was weaker and not clearly detectable under the present conditions. Control assays showed no significant effects of diazepam on threat or reward memory retrieval, sucrose intake, open-field locomotion, or anxiety-like behavior.

These findings indicate that diazepam shifts behavioral allocation toward reward during threat-reward conflict and alters post-conflict avoidance re-expression, with effects that were more apparent in males than in females, while sparing reactive avoidance under no-conflict conditions.