Prefrontal cortical dopamine depletion enhances the responsiveness of mesolimbic dopamine neurons to stress

Mild footshock stress results in the metabolic activation of the prefrontal cortical dopamine (DA) innervation, but does not augment DA utilization in mesolimbic areas (such as the nucleus accumbens septi, NAS) or the striatum. However, increases in either the intensity or duration of footshock stress increase DA utilization in the subcortical sites. DA afferents to the prefrontal cortex (PFC) hold corticofugal projection neurons under tonic inhibition. Previous data suggest that removal of these corticofugal glutamatergic neurons from tonic DA inhibition results in a transsynaptic alteration in the NAS, such that the DA innervation of the NAS is rendered hyperresponsive to certain perturbations. We therefore examined the effects of stress on subcortical DA systems in rats previously subjected to 6-hydroxydopamine lesions of the PFC DA innervation. Mild footshock stress resulted in an increase in concentrations of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the PFC, but not NAS or striatum, of sham-lesioned animals. Footshock resulted in a significant increase in the concentration of DOPAC in the nucleus accumbens of animals sustaining PFC lesions two weeks previously. The PFC lesion did not result in a stress-induced increase in DA release in the striatum. These results suggest that disruption of the PFC DA innervation results in an enhanced responsiveness of the mesolimbic DA innervation to stress. These data may help explain the stress-elicited exacerbation of the psychotic process in schizophrenia.

[1]  K. Davis,et al.  Effects of mesocortical dopaminergic lesions upon subcortical dopaminergic function. , 1988, Psychopharmacology bulletin.

[2]  J. Coyle,et al.  N‐Acetyl‐Aspartyl‐Glutamate: Regional Levels in Rat Brain and the Effects of Brain Lesions as Determined by a New HPLC Method , 1984, Journal of neurochemistry.

[3]  J. Glowinski,et al.  Selective activation of the mesocortical DA system by stress , 1976, Nature.

[4]  C. Carter,et al.  Behavioural and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat , 1980, Brain Research.

[5]  Y. Claustre,et al.  Pharmacological studies on stress-induced increase in frontal cortical dopamine metabolism in the rat. , 1986, The Journal of pharmacology and experimental therapeutics.

[6]  R. Roth,et al.  The effects of perinatal diazepam exposure on stress-induced activation of the mesotelencephalic dopamine system. , 1989, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[7]  P. Duffy,et al.  Regulation of the mesocorticolimbic dopamine system by glutamic acid receptor subtypes. , 1989, The Journal of pharmacology and experimental therapeutics.

[8]  R. Dantzer,et al.  Differential effects of inescapable footshocks and of stimuli previously paired with inescapable footshocks on dopamine turnover in cortical and limbic areas of the rat. , 1982, Life sciences.

[9]  A. Dunn.  Stress‐Related Activation of Cerebral Dopaminergic Systems a , 1988, Annals of the New York Academy of Sciences.

[10]  W. Lyness,et al.  Lesions of dopamine neurons in the medial prefrontal cortex: Effects on self-administration of amphetamine and dopamine synthesis in the brain of the rat , 1987, Neuropharmacology.

[11]  H. Simon,et al.  Mesencephalic Dopaminergic Neurons: Role in the General Economy of the Brain , 1988, Annals of the New York Academy of Sciences.

[12]  B. Bunney,et al.  Pharmacological characterization of the receptor mediating electrophysiological responses to dopamine in the rat medial prefrontal cortex: a microiontophoretic study. , 1989, The Journal of pharmacology and experimental therapeutics.

[13]  J. Girault,et al.  In Vivo Release of Endogenous Amino Acids from the Rat Striatum: Further Evidence for a Role of Glutamate and Aspartate in Corticostriatal Neurotransmission , 1986, Journal of neurochemistry.

[14]  H. Mount,et al.  Glutamate Stimulation of [3H]Dopamine Release from Dissociated Cell Cultures of Rat Ventral Mesencephalon , 1989, Journal of neurochemistry.

[15]  D. Weinberger.  Implications of normal brain development for the pathogenesis of schizophrenia. , 1987, Archives of general psychiatry.

[16]  R. Roth,et al.  The use of c8-octyl columns for the analysis of catecholamines by ion-pair reversed-phase liquid chromatography with amperometric detection. , 1981, Journal of chromatography.

[17]  R. Roth,et al.  The anxiogenic β-carboline FG-7142 increases in vivo and in vitro tyrosine hydroxylation in the prefrontal cortex , 1989, Brain Research.

[18]  M. Le Moal,et al.  Locomotor activity in relation to dopamine and noradrenaline in the nucleus accumbens, septal and frontal areas: a 6-hydroxydopamine study. , 2008, Neuropsychobiology.

[19]  B. Scatton,et al.  An in Vivo Voltammetric Study of the Response of Mesocortical and Mesoaccumbens Dopaminergic Neurons to Environmental Stimuli in Strains of Rats with Differing Levels of Emotionality , 1988, Annals of the New York Academy of Sciences.

[20]  R. Roth,et al.  The determinants of stress-induced activation of the prefrontal cortical dopamine system. , 1990, Progress in brain research.

[21]  C. Carter.  Topographical distribution of possible glutamatergic pathways from the frontal cortex to the striatum and substantia nigra in rats , 1982, Neuropharmacology.

[22]  L. Swanson,et al.  The projections of the ventral tegmental area and adjacent regions: A combined fluorescent retrograde tracer and immunofluorescence study in the rat , 1982, Brain Research Bulletin.

[23]  R. Roth,et al.  Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: An anterograde tract‐tracing study with Phaseolus vulgaris leucoagglutinin , 1989, The Journal of comparative neurology.

[24]  A. Mcgeorge,et al.  The organization of the projection from the cerebral cortex to the striatum in the rat , 1989, Neuroscience.

[25]  M. J. Christie,et al.  Excitotoxin lesions suggest an aspartatergic projection from rat medial prefrontal cortex to ventral tegmental area , 1985, Brain Research.

[26]  R. Roth,et al.  Stress and the Mesocorticolimbic Dopamine Systems a , 1988, Annals of the New York Academy of Sciences.

[27]  D. Lysle,et al.  Stress and Enhanced Dopamine Utilization in the Frontal Cortex: The Myth and the Reality a , 1988, Annals of the New York Academy of Sciences.

[28]  M. Le Moal,et al.  Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on the dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study , 1989, Neuroscience.

[29]  B. Bunney,et al.  Dopamine and norepinephrine innervated cells in the rat prefrontal cortex: pharmacological differentiation using microiontophoretic techniques. , 1976, Life sciences.

[30]  A. Hamberger,et al.  In Vivo Studies on the Extracellular, and Veratrine‐Releasable, Pools of Endogenous Amino Acids in the Rat Striatum: Effects of Corticostriatal Deafferentation and Kainic Acid Lesion , 1987, Journal of neurochemistry.

[31]  R. Roth,et al.  Footshock and conditioned stress increase 3, 4-dihydroxyphenylacetic acid (DOPAC) in the ventral tegmental area but not substantia nigra , 1985, Brain Research.

[32]  J. Glowinski,et al.  Influence of the Mesocortical/Prefrontal Dopamine Neurons on Their Target Cells a , 1988, Annals of the New York Academy of Sciences.

[33]  P. Roberts,et al.  STIMULATORY EFFECT OF l‐GLUTAMATE AND RELATED AMINO ACIDS ON [3H]DOPAMINE RELEASE FROM RAT STRIATUM: AN IN VITRO MODEL FOR GLUTAMATE ACTIONS , 1979, Journal of neurochemistry.