Systemic Propranolol Acts Centrally to Reduce Conditioned Fear in Rats Without Impairing Extinction

Background

Previous work has implicated noradrenergic β-receptors in the consolidation and reconsolidation of conditioned fear. Less is known, however, about their role in fear expression and extinction. The β-receptor blocker propranolol has been used clinically to reduce anxiety. With an auditory fear conditioning task in rats, we assessed the effects of systemic propranolol on the expression and extinction of two measures of conditioned fear: freezing and suppression of bar-pressing.

Methods

One day after receiving auditory fear conditioning, rats were injected with saline, propranolol, or peripheral β-receptor blocker sotalol (both 10 mg/kg, IP). Twenty minutes after injection, rats were given either 6 or 12 extinction trials and were tested for extinction retention the following day. The effect of propranolol on the firing rate of neurons in prelimbic (PL) prefrontal cortex was also assessed.

Results

Propranolol reduced freezing by more than 50%, an effect that was evident from the first extinction trial. Suppression was also significantly reduced. Despite this, propranolol had no effect on the acquisition or retention of extinction. Unlike propranolol, sotalol did not affect fear expression, although both drugs significantly reduced heart rate. This suggests that propranolol acts centrally to reduce fear. Consistent with this, propranolol reduced the firing rate of PL neurons.

Conclusion

Propranolol reduced the expression of conditioned fear, without interfering with extinction learning. Reduced fear with intact extinction suggests a possible use for propranolol in reducing anxiety during extinction-based exposure therapies, without interfering with long-term clinical response.

Key Words: Anxiety disorder, heart rate, noradrenergic, prefrontal, prelimbic, PTSD