The impact of systemic blockade of dopamine receptors on the acquisition of two-way active avoidance in male rats

Active threat avoidance is a core aspect of adaptive and maladaptive behavior, yet its underlying mechanisms are not fully understood. Prior studies concluded that pharmacologically blocking dopaminergic receptors (DRs) disrupted avoidance acquisition, but it remains unclear whether such effects on learning persist during a drug-free follow-up test. To assess the involvement of D1R and D2R in avoidance acquisition, we conducted two experiments. In Experiment 1, thirty-six male Wistar rats underwent a single avoidance training session involving 30 tone-shock pairings. Rats could avoid the shock by moving to the opposite compartment of the shuttle box. Twenty minutes before training, rats received either D1R antagonist SCH 23390 (0.05 mg/kg), D2R antagonist sulpiride (20 mg/kg), or vehicle. While sulpiride did not affect avoidance, 0.05 mg/kg SCH 23390 significantly reduced the number of avoidance responses. In a separate test, 0.05 mg/kg SCH 23390 also reduced locomotor activity. In Experiment 2 (N = 24), a lower dose of SCH 23390 (0.025 mg/kg) was administered, and a drug-free avoidance test under continued reinforcement was added 24 h later to test for sustained effects of D1R blockade on avoidance in the absence of acute drug effects. Although animals avoided less with SCH 23390 in the system, this effect did not persist 24 h later, suggesting that effects of D1R blockade during avoidance training might reflect an acute disruption of secondary processes involved in the performance of avoidance behavior rather than an actual impairment of avoidance learning.