Articles

Dopaminergic Activity in the Medial Prefrontal Cortex Modulates Fear Conditioning

Abstract

The purpose of the present study was to determine the role of medial prefrontal cortex (mPFC) dopaminergic system in fear conditioning response considering individual differences. Animals were initially counterbalanced and classified based on open field test, and then were given a single infusion of the dopamine agonist, amphetamine (AMPH) and antagonist, clozapine (CLZ) into the medial prefrontal cortex. Rats received tone-shock pairing in a classical fear conditioning test and then exposed to the tone alone. Freezing responses were measured as conditioned fear index. The results showed that both AMPH and CLZ infusion in mPFC reduced the expression of conditioned fear. This finding indicates that elevation or reduction in the dopaminergic activity is associated with the decrease of fear responses, despite preexisting individual-typological differences.

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(6):728-33.

Corcoran KA, Quirk GJ. Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears. J Neurosci 2007;27(4):840-4.

Hugues S, Deschaux O, Garcia R. Postextinction infusion of a mitogen-activated protein kinase inhibitor into the medial prefrontal cortex impairs memory of the extinction of conditioned fear. Learn Mem 2004;11(5):540-3.

Hikind N, Maroun M. Microinfusion of the D1 receptor antagonist, SCH23390 into the IL but not the BLA impairs consolidation of extinction of auditory fear conditioning. Neurobiol Learn Mem 2008;90(1):217-22.

Hurley KM, Herbert H, Moga MM, Saper CB. Efferent projections of the infralimbic cortex of the rat. J Comp Neurol 1991;308(2):249-76.

LeDoux JE, Iwata J, Cicchetti P, Reis DJ. Different projections of the central amygdaloid nucleus mediateautonomic and behavioral correlates of conditioned fear. J Neurosci 1988;8(7):2517-29.

McDonald AJ. Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat. Neuroscience 1991;44(1):1-14.

Amorapanth P, LeDoux JE, Nader K. Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus. Nat Neurosci 2000;3(1):74-9.

Morgan MA, LeDoux JE. Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behav Neurosci 1995;109(4):681-8.

Quirk GJ, Russo GK, Barron JL, Lebron K. The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J Neurosci 2000;20(16):6225-31.

Strekalova TV. The characteristics of the defensive behavior of rats in accordance with their resistance to emotional stress. Zh Vyssh Nerv Deiat Im I P Pavlova 1995;45(2):420-2.

Anokhina IP. Neurohumoral factors of individual resistance against emotional stress. In: Anokhina IP. Motivatsiya I Emotsional'nyi Stress (Motivation and Emotional Stress). Moscow: Nauka; 1987. part 2. p. 3-8.

Babai P, Anokhin KV, Dolgov N, Sudakov KV. Characteristics of c-fos gene expression in the brains of rats with different investigative and defensive behaviors. Neurosci Behav Physiol 2001;31(6):583-8.

Garpenstrand H, Annas P, Ekblom J, Oreland L, Fredrikson M. Human fear conditioning is related to dopaminergic and serotonergic biological markers. Behav Neurosci 2001;115(2):358-64.

Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 4th ed. San Diego, CA: Academic Press; 1998.

Compton AD, Slemmer JE, Drew MR, Hyman JM, Golden KM, Balster RL, Wiley JL. Combinations of clozapine and phencyclidine: effects on drug discrimination and behavioral inhibition in rats. Neuropharmacology 2001;40(2):289-97.

Pezze MA, Feldon J. Mesolimbic dopaminergic pathways in fear conditioning. Prog Neurobiol 2004;74(5):301-20.

D'Angio M, Serrano A, Driscoll P, Scatton B. Stressful environmental stimuli increase extracellular DOPAC levels in the prefrontal cortex of hypoemotional (Roman high-avoidance) but not hyperemotional (Roman lowavoidance) rats. An in vivo voltammetric study. Brain Res 1988;451(1-2):237-47.

Giorgi O, Lecca D, Piras G, Driscoll P, Corda MG. Dissociation between mesocortical dopamine release and fear-related behaviours in two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions. Eur J Neurosci 2003;17(12):2716-26.

Siemiatkowski M, Rokicki D, Członkowska AI, Sienkiewicz-Jarosz H, Bidziński A, Płaźnik A. Locomotor activity and a conditioned fear response: correlation withcortical and subcortical binding of the dopamine D1 receptor antagonist. Neuroreport 2000;11(18):3953-6.

Quirk GJ, Garcia R, González-Lima F. Prefrontal mechanisms in extinction of conditioned fear. Biol Psychiatry 2006;60(4):337-43.

Gewirtz JC, Falls WA, Davis M. Normal conditioned inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medical prefrontal cortex in rats. Behav Neurosci 1997;111(4):712-26.

Files
IssueVol 49, No 7 (2011) QRcode
SectionArticles
Keywords
Dopamine Fear conditioning Individuality Open field mPFC

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Babaei P, Soltani Tehrani B, Alizadeh A, Nakhostin M. Dopaminergic Activity in the Medial Prefrontal Cortex Modulates Fear Conditioning. Acta Med Iran. 1;49(7):433-437.