Biological Psychiatry
Volume 65, Issue 10 , Pages 887-892 , 15 May 2009

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

  • Jose Rodriguez-Romaguera

      Affiliations

    • Department of Psychology Undergraduate Program, University of Puerto Rico, San Juan, Puerto Rico
    • ,
  • Francisco Sotres-Bayon

      Affiliations

    • Department of Psychiatry and Anatomy & Neurobiology, University of Puerto Rico, San Juan, Puerto Rico
    • ,
  • Devin Mueller

      Affiliations

    • Department of Psychiatry and Anatomy & Neurobiology, University of Puerto Rico, San Juan, Puerto Rico
    • Corresponding Author InformationAddress reprint requests to Devin Mueller, Ph.D., Department of Psychology, University of Wisconsin-Milwaukee, P.O. Box 413, Milwaukee, WI 53201
    • ,
  • Gregory J. Quirk

      Affiliations

    • Department of Psychiatry and Anatomy & Neurobiology, University of Puerto Rico, San Juan, Puerto Rico

Received 3 December 2008 ,Revised 4 January 2009 ,Accepted 7 January 2009.

References 

  1. McGaugh JL. Memory—a century of consolidation. Science. 2000;287:248–251
  2. Cahill L, Prins B, Weber M, McGaugh JL. Beta-adrenergic activation and memory for emotional events. Nature. 1994;371:702–704
  3. Hatfield T, McGaugh JL. Norepinephrine infused into the basolateral amygdala posttraining enhances retention in a spatial water maze task. Neurobiol Learn Mem. 1999;71:232–239
  4. Debiec J, LeDoux JE. Disruption of reconsolidation but not consolidation of auditory fear conditioning by noradrenergic blockade in the amygdala. Neuroscience. 2004;129:267–272
  5. Brantigan CO, Brantigan TA, Joseph N. Effect of beta blockade and beta stimulation on stage fright. Am J Med. 1982;72:88–94
  6. Faigel HC. The effect of beta blockade on stress-induced cognitive dysfunction in adolescents. Clin Pediatr (Phila). 1991;30:441–445
  7. Grillon C, Cordova J, Morgan CA, Charney DS, Davis M. Effects of the beta-blocker propranolol on cued and contextual fear conditioning in humans. Psychopharmacology (Berl). 2004;175:342–352
  8. Angrini M, Leslie JC, Shephard RA. Effects of propranolol, buspirone, pCPA, reserpine, and chlordiazepoxide on open-field behavior. Pharmacol Biochem Behav. 1998;59:387–397
  9. Walker DL, Davis M. Light-enhanced startle: Further pharmacological and behavioral characterization. Psychopharmacology (Berl). 2002;159:304–310
  10. Davis M, Redmond DE, Baraban JM. Noradrenergic agonists and antagonists: Effects on conditioned fear as measured by the potentiated startle paradigm. Psychopharmacology (Berl). 1979;65:111–118
  11. Cain CK, Blouin AM, Barad M. Adrenergic transmission facilitates extinction of conditional fear in mice. Learn Mem. 2004;11:179–187
  12. Cassens G, Roffman M, Kuruc A, Orsulak PJ, Schildkraut JJ. Alterations in brain norepinephrine metabolism induced by environmental stimuli previously paired with inescapable shock. Science. 1980;209:1138–1140
  13. Hugues S, Garcia R, Lena I. Time course of extracellular catecholamine and glutamate levels in the rat medial prefrontal cortex during and after extinction of conditioned fear. Synapse. 2007;61:912–916
  14. Erb S, Hitchcott PK, Rajabi H, Mueller D, Shaham Y, Stewart J. Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking. Neuropsychopharmacology. 2000;23:138–150
  15. Mueller D, Porter JT, Quirk GJ. Noradrenergic signaling in infralimbic cortex increases cell excitability and strengthens memory for fear extinction. J Neurosci. 2008;28:369–375
  16. Vidal-Gonzalez I, Vidal-Gonzalez B, Rauch SL, Quirk GJ. Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learn Mem. 2006;13:728–733
  17. Blum S, Hebert AE, Dash PK. A role for the prefrontal cortex in recall of recent and remote memories. Neuroreport. 2006;17:341–344
  18. Corcoran KA, Quirk GJ. Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears. J Neurosci. 2007;27:840–844
  19. Cahill SP, Foa EB, Hembree EA, Marshall RD, Nacash N. Dissemination of exposure therapy in the treatment of posttraumatic stress disorder. J Trauma Stress. 2006;19:597–610
  20. Quirk GJ, Russo GK, Barron JL, Lebron K. The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J Neurosci. 2000;20:6225–6231
  21. Dahlof C. Studies on beta-adrenoceptor mediated facilitation of sympathetic neurotransmission. Acta Physiol Scand Suppl. 1981;500:1–147
  22. Blanchard DC, Blanchard RJ. Innate and conditioned reactions to threat in rats with amygdaloid lesions. J Comp Physiol Psychol. 1972;81:281–290
  23. Estes WK, Skinner BF. Some quantitative properties of anxiety. J Exp Psychol. 1941;29:390–400
  24. Burgos-Robles A, Vidal-Gonzalez I, Santini E, Quirk GJ. Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex. Neuron. 2007;53:871–880
  25. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 6th edition. Amsterdam: Elsevier; 2007;
  26. Nakano J, Kusakari T. Effect of beta adrenergic blockade on the cardiovascular dynamics. Am J Physiol. 1966;210:833–837
  27. Arendt RM, Greenblatt DJ, deJong RH, Bonin JD, Abernethy DR. Pharmacokinetics, central nervous system uptake, and lipid solubility of propranolol, acebutolol, and sotalol. Cardiology. 1984;71:307–314
  28. Morris RW, Westbrook RF, Killcross AS. Reinstatement of extinguished fear by beta-adrenergic arousal elicited by a conditioned context. Behav Neurosci. 2005;119:1662–1671
  29. Ouyang M, Thomas SA. A requirement for memory retrieval during and after long-term extinction learning. Proc Natl Acad Sci U S A. 2005;102:9347–9352
  30. Berlau DJ, McGaugh JL. Enhancement of extinction memory consolidation: the role of the noradrenergic and GABAergic systems within the basolateral amygdala. Neurobiol Learn Mem. 2006;86:123–132
  31. Gilmartin MR, McEchron MD. Single neurons in the medial prefrontal cortex of the rat exhibit tonic and phasic coding during trace fear conditioning. Behav Neurosci. 2005;119:1496–1510
  32. Vidal-Gonzalez I, Corcoran KA, Vidal-Gonzalez B, Rauch SL, Quirk GJ. Converging pharmacological, microstimulation, and physiological evidence that the prelimbic prefrontal cortex mediates expression of learned fears in the rat. Neuropsychopharmacology. 2006;31:S161
  33. Buffalari DM, Grace AA. Noradrenergic modulation of basolateral amygdala neuronal activity: Opposing influences of alpha-2 and beta receptor activation. J Neurosci. 2007;27:12358–12366
  34. Choy Y, Fyer AJ, Lipsitz JD. Treatment of specific phobia in adults. Clin Psychol Rev. 2007;27:266–286
  35. Davis M, Myers KM, Chhatwal J, Ressler KJ. Pharmacological treatments that facilitate extinction of fear: Relevance to psychotherapy. NeuroRx. 2006;3:82–96
  36. Bouton ME, Kenney FA, Rosengard C. State-dependent fear extinction with two benzodiazepine tranquilizers. Behav Neurosci. 1990;104:44–55
  37. Tyrer P. Current status of beta-blocking drugs in the treatment of anxiety disorders. Drugs. 1988;36:773–783
  38. Liu HH, Milgrom P, Fiset L. Effect of a beta-adrenergic blocking agent on dental anxiety. J Dent Res. 1991;70:1306–1308
  39. Ravaris CL, Friedman MJ, Hauri PJ, McHugo GJ. A controlled study of alprazolam and propranolol in panic-disordered and agoraphobic outpatients. J Clin Psychopharmacol. 1991;11:344–350
  40. Fagerstrom KO, Hugdahl K, Lundstrom N. Effect of beta-receptor blockade on anxiety with reference to the three-systems model of phobic behavior. Neuropsychobiology. 1985;13:187–193
  41. Alexander JK, Hillier A, Smith RM, Tivarus ME, Beversdorf DQ. Beta-adrenergic modulation of cognitive flexibility during stress. J Cogn Neurosci. 2007;19:468–478
  42. Do Monte FH, Canteras NS, Fernandes D, Assreuy J, Carobrez AP. New perspectives on beta-adrenergic mediation of innate and learned fear responses to predator odor. J Neurosci. 2008;28:13296–13302

PII: S0006-3223(09)00034-1

doi: 10.1016/j.biopsych.2009.01.009

Biological Psychiatry
Volume 65, Issue 10 , Pages 887-892 , 15 May 2009

Article Tools

* Image Usage & Resolution