Review
Amygdalar control of the mesocorticolimbic dopamine system: parallel pathways to motivated behavior

https://doi.org/10.1016/j.neubiorev.2003.09.002Get rights and content

Abstract

The present review focuses on recent findings from our laboratory showing that there are major differences in the influence exerted by the central (CeN) and basolateral (BLA) nuclei of the amygdala on dopamine (DA) efflux in the nucleus accumbens (NAc) of the rat. Based on these data, we propose that the CeN maintains control, via an indirect pathway, of the tonic activity of a population of ventral tegmental dopamine neurons that specifically regulate basal DA efflux in the NAc. Related experiments also support the hypothesis that control of mesocorticolimbic DA activity by the CeN can influence the incentive value of the sensory property of food and its modulation by the drive-state of the animal. In contrast, we suggest that activation of the BLA can evoke transient increases in DA efflux in the NAc and medial prefrontal cortex (mPFC) and may also stabilize the activity of dopaminergic neurons projecting to the mPFC. We hypothesize that the rapid transient regulation of DA efflux in the NAc by the BLA plays an essential role in the selection and co-ordination of specific sequences of behaviors appropriate to incentive stimuli present in the environment. In this manner, the amygdala may exert differential control on motivated behavior, thereby ensuring the selection of behavioral responses that are optimal for survival.

Section snippets

Introduction: parallel processing in the amygdala

Prominent theories of amygdalar function have emphasized the importance of a serial flow of information from the lateral nucleus to the central nucleus (CeN) of the amygdala [1], [2]. This position is based primarily on models of the neural substrates of fear conditioning, which postulate that this circuit is critical for establishing conditioned responses to a perceived threat, as demonstrated in conditioned freezing and fear-potentiated startle paradigms [2], [3], [4], [5]. An alternative

Effects of transient blockade of sodium channels

Given the evidence that the CeN may send inhibitory polysynaptic projections to midbrain areas populated by DA neurons and that the BLA sends monosynaptic excitatory afferents to regions innervated by DA terminals, we investigated whether the CeN and/or the BLA can influence basal rates of DA efflux in both the NAc and mPFC [46]. Neural activity was blocked temporarily by reverse-dialysis of the sodium channel blocker lidocaine (2%) into either the CeN or BLA. Lidocaine is a sodium channel

Empirical evidence

In addition to observing the effects of transient inactivation of the CeN or BLA on basal DA efflux in the NAc and mPFC (Fig. 1), we have examined feeding behavior during a small meal of palatable food (3 g Froot Loops™) under the same conditions [46]. Rats that were reverse-dialyzed with lidocaine into the CeN (50 min) manipulated and tasted every morsel of food in their mouths, but ingested less than 50% and emitted the remaining amount (Fig. 3). Animals tested in the control condition (i.e.

Conclusions

The present paper has reviewed recent evidence from our laboratory addressing the roles of both the BLA and CeN in modulating basal and evoked DA efflux in the NAc and mPFC. Generally, these data suggest differential roles of the CeN and BLA in modulating forebrain DA efflux. On the basis of data from both the stimulation and inactivation experiments, the CeN appears to play a role in the tonic modulation of DA efflux in the NAc, whereas activation of the BLA causes rapid and transient

Acknowledgements

This research was funded by a grant from the Canadian Institutes for Health Research to AGP. JGH was funded by a K.M. Hunter/Canadian Institutes for Health Research Doctoral Training Award.

References (90)

  • T Uwano et al.

    Neuronal responsiveness to various sensory stimuli, and associative learning in the rat amygdala

    Neuroscience

    (1995)
  • R.P Kesner et al.

    Central but not basolateral amygdala mediates memory for positive affective experiences

    Behav Brain Res

    (1989)
  • J.A Salinas et al.

    Ibotenic acid lesions of the amygdala basolateral complex or central nucleus differentially effect the response to reductions in reward

    Brain Res

    (1996)
  • S Ahn et al.

    Independent modulation of basal and feeding-evoked dopamine efflux in the nucleus accumbens and medial prefrontal cortex by the central and basolateral amygdalar nuclei in the rat

    Neuroscience

    (2003)
  • E.J Tehovnik et al.

    Effect of spread and time course of neural inactivation caused by lidocaine injection in monkey cerebral cortex

    J Neurosci Meth

    (1997)
  • S.E Boehnke et al.

    Time course and effect of spread of lidocaine and tetrodotoxin delivered via microdialysis: an electrophysiological study in cerebral cortex

    J Neurosci Meth

    (2001)
  • A.J Silva et al.

    Molecular and cellular mechanisms of cognitive function: implications for psychiatric disorders

    Biol Psychiatry

    (2000)
  • K Sato et al.

    The differential expression patterns of messenger RNAs encoding non-N-methyl-d-aspartate glutamate receptor subunits (GluR1-4) in the rat brain

    Neuroscience

    (1993)
  • K.N Gracy et al.

    Ultrastructural immounocytochemical localization of the N-methyl-d-aspartate receptor and tyrosine hydroxylase in the shell of the rat nucleus accumbens

    Brain Res

    (1996)
  • J.M Desce et al.

    l-glutamate-evoked release of dopamine from synaptosomes of the rat striatum: involvement of AMPA and N-methyl-d-aspartate receptors

    Neuroscience

    (1992)
  • A Imperato et al.

    NMDA receptors and in vivo dopamine release in the nucleus accumbens and caudatus

    Eur J Pharmacol

    (1990)
  • B.B Ruzicka et al.

    Excitatory amino acid action on the release of brain neurotransmitters and neuromodulators: biochemical studies

    Prog Neurobiol

    (1993)
  • E.D French et al.

    Phencyclidine binding sites in the nucleus accumbens and phencyclidine-induced hyperactivity are decreased following lesions of the mesolimbic dopamine system

    Eur J Pharmacol

    (1985)
  • K Zavitsanou et al.

    Changes in [3H]AMPA and [3H]kainate binding in rat caudate-putamen and nucleus accumbens after 6-hydroxydopamine lesions of the medial forebrain bundle: an autoradiographic study

    Brain Res

    (1996)
  • H Maeda et al.

    Electrophysiological responses of neurons of the ventral tegmental area to electrical stimulation of the amygdala and lateral septum

    Neuroscience

    (1981)
  • M.F Suaud-Chagny et al.

    Relationship between dopamine release in the rat nucleus accumbens and the discharge activity of dopaminergic neurons during local in vivo application of amino acids in the ventral tegmental area

    Neuroscience

    (1992)
  • J Fadel et al.

    Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area

    Neuroscience

    (2002)
  • A.A Grace

    Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia

    Neuroscience

    (1991)
  • K.C Berridge et al.

    What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?

    Brain Res Rev

    (1998)
  • W Schultz et al.

    Reward prediction in primate basal ganglia and frontal cortex

    Neuropharmacology

    (1998)
  • O.G Galaverna et al.

    Lesions of the central nucleus of the amygdala I: effects on taste reactivity, taste aversion learning and sodium appetite

    Behav Brain Res

    (1993)
  • A.G Phillips et al.

    Conditioned aversion to brain stimulation reward: effects of electrode placement and prior experience

    Brain Res

    (1979)
  • L.H Burns et al.

    Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of d-amphetamine

    Behav Brain Res

    (1993)
  • M Davis

    The role of the amygdala in conditioned fear

  • J.E LeDoux

    Emotion circuits in the brain

    Annu Rev Neurosci

    (2000)
  • P Amorapanth et al.

    Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus

    Nat Neurosci

    (2000)
  • C.B Sananes et al.

    N-methyl-d-aspartate lesions of the lateral and basolateral nuclei of the amygdala block fear-potentiated startle and shock sensitization of startle

    Behav Neurosci

    (1992)
  • B.J Everitt et al.

    Differential involvement of amygdala subsystems in appetitive conditioning and drug addiction

  • S Killcross et al.

    Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala

    Nature

    (1997)
  • P.J Kruzich et al.

    Differential contributions of the basolateral and central amygdala in the acquisition and expression of conditioned relapse to cocaine-seeking behavior

    J Neurosci

    (2001)
  • A.J McDonald

    Neurons of the lateral and basolateral amygdaloid nuclei: a golgi study in the rat

    J Comp Neurol

    (1982)
  • O.P Otterson

    Connections of the amygdala of the rat. IV. Corticoamygdaloid and intraamygdaloid connections as studied with axonal transport of horseradish peroxidase

    J Comp Neurol

    (1982)
  • A.J McDonald

    Is there an amygdala and how far does it extend? An anatomical perspective

    Ann NY Acad Sci

    (2003)
  • R Norgren

    Taste pathways to hypothalamus and amygdala

    J Comp Neurol

    (1976)
  • J.L Price

    Comparative aspects of amygdala connectivity

    Ann NY Acad Sci

    (2003)
  • Cited by (142)

    • Amygdala circuits

      2022, Neurocircuitry of Addiction
    View all citing articles on Scopus
    View full text