Role of dopamine receptor mechanisms in the amygdaloid modulation of fear and anxiety: Structural and functional analysis
Introduction
There is a general agreement that anxiety is an adaptive response which detects and prepares an individual against a real or a potential threat. Since according to this definition anxiety is concerned with defense responses (Blanchard and Blanchard, 1969, Blanchard and Blanchard, 1989, Bolles, 1970, Blanchard et al., 1977, Blanchard et al., 1989, Blanchard et al., 1993, Pinel and Treit, 1978, Rodgers, 1997, McNaughton and Corr, 2004) it is not surprising that a number of brain regions have been advocated in its modulation and particularly those regions which have been evolutionarily conserved (McNaughton and Corr, 2004). Among these neural structures the amygdala seems to be of paramount importance for the modulation of fear and anxiety (for reviews see: McGaugh et al., 1992, Gray and McNaughton, 2000, LeDoux, 2000, Singewald and Sharp, 2000, Davis and Whalen, 2001, Davidson, 2002, Everitt et al., 2003, Millan, 2003, Paré et al., 2004, Pezze and Feldon, 2004, Ressler and Mayberg, 2007, Engin and Treit, 2008, Pérez de la Mora et al., 2008).
Many neurotransmitters with their receptors participate in the modulation of anxiety (for reviews see: Menard and Treit, 1999, Davis and Whalen, 2001, De Boer and Koolhaas, 2003, File and Seth, 2003, Millan, 2003, Engin and Treit, 2008). The GABAergic and glutamatergic systems are responsible for the main inhibitory and excitatory drives respectively in the mammalian central nervous system and their role in fear and anxiety have been studied extensively (Davis and Whalen, 2001, Millan, 2003, Engin and Treit, 2008). Modulatory neuronal systems such as the dopaminergic one have received less attention.
The aim of this work is to review the participation of the dopaminergic system in the modulatory influence that the amygdala exerts on fear and anxiety paying particular attention to the anatomical distribution of the dopaminergic system within the amygdala, and to the role that the dopamine (DA) D1 and D2 receptors play in this phenomenon. Papers specifically reviewing the role of dopamine on anxiety from a different perspective have already been published (Blackburn et al., 1992, Pezze and Feldon, 2004, Engin and Treit, 2008). The expression of fear and anxiety is experimentally indistinguishable in animals in spite of the fact that there may exist some conceptual and mechanistic differences between them (LeDoux, 1992, McNaughton and Corr, 2004). In this review we will refer to them interchangeably. Likewise, we will refer to conditioned and unconditioned fear as the fear that is measured in conditioned and non-conditioned tests of fear and anxiety, respectively.
Section snippets
Amygdala
After the seminal work of Kluver and Bucy, 1937, Kluver and Bucy, 1939 showing that monkeys with large lesions of the temporal lobe developed a bizarre behavior characterized by signs of hypoemotionality and loss of fear to inanimate objects and animate subjects including their keepers and dominant monkeys (Weiskrantz, 1956, Kling and Brothers, 1992), evidence was published suggesting that the amygdala was responsible for such a behavior. A common agreement was reached that this brain region
Classification
Dopamine receptors belong to the seven transmembrane domain G-protein-coupled receptor family and have been classified on the basis of biochemical, pharmacological and physiological criteria in two types, D1 and D2 receptors (Kebabian and Calne, 1979). Subsequent cloning experiments showed that D1 and D2 receptors were not single molecular entities but two different dopamine receptor families (for a review see Sokoloff and Schwartz, 1995, Missale et al., 1998). Thus D1 receptor family is
The mesoamygdaloid dopamine pathway
By means of the method developed by Nils-Åke Hillarp and Bengt Falck in Sweden for the visualization of catecholamines and 5-HT (Falck et al., 1962), Dahlström and Fuxe (1964) showed for the first time in their now classical paper published in the Acta Physiologica Scandinavica the existence of two distinct populations of dopamine cell bodies within the rat ventral mesencephalon. These DA cell masses according to their original classification were designated as the A9 and A10 catecholamine cell
The mesoamygdaloid dopamine pathway
As discussed above, the amygdala is maintained under the control of the medial prefrontal cortex but under the pressure of environmental threats dopaminergic neurotransmission restores its activity allowing the development of anxiety responses (Rosenkranz and Grace, 1999, Rosenkranz and Grace, 2002a, Kröner et al., 2005, Marowsky et al., 2005) and the gating of LTP induction (Rosenkranz and Grace, 2002b, Bissiere et al., 2003). On this scenery, the mesoamygdaloid dopamine pathway provides the
Conclusions
From the experimental evidence reviewed here it can be concluded that amygdala is strongly but differentially innervated by the mesoamygdaloid dopamine pathway. Through the release of dopamine at topographically non-overlapping dopamine D1- and D2-receptor binding sites these DA amygdaloid nerve terminal systems release the amygdala from its mPFC brake and prepares the individual to cope with real or potential threats from its environment. As the D1 receptor is the main type of dopamine
Acknowledgements
The help of Minerva Crespo-Ramírez in the preparation of this manuscript is fully appreciated. This work was supported in part by the grant IN200508 from Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (UNAM) and by a grant from the Swedish Research Council.
References (298)
- et al.
Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta)
Brain Res.
(1980) - et al.
Receptor mosaics of neural and immune communication: possible implications for basal ganglia functions
Brain Res. Rev.
(2008) - et al.
New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata
Neuroscience
(1988) - et al.
Demonstration and mapping out of nigro-neostriatal dopamine neurons
Life Sci.
(1964) - et al.
Mapping out of catecholamine and 5-hydroxytryptamine neurons innervating the telencephalon and diencephalon
Life Sci.
(1965) Comparison of the pharmacological characteristics of [3H] raclopride and SCH23390 binding to dopaminereceptors in vivo in mouse brain
Eur. J. Pharmacol.
(1988)- et al.
Partial and full dopamine D1 receptor agonists in mice and rats: relation between behavioural effects and stimulation of adenylate cyclase activity in vitro
Eur. J. Pharmacol.
(1992) - et al.
Comparison of different behavioral test situations used in psychopharmacology for measurement of anxiety
Physiol. Behav.
(1994) - et al.
Dopamine functions in appetitive and defensive behaviours
Prog. Neurobiol.
(1992) - et al.
Attack and defensive behavior in the albino rat
Anim. Behav.
(1977)
Defense system psychopharmacology: an ethological approach to the pharmacology of fear and anxiety
Behav. Brain Res.
A detailed mapping of dopamine D-2 receptors in rat central nervous system by autoradiography with [125I]iodosulpride
Neuroscience
Evidence that dopaminergic axons provide a dense innervations of specific neuronal subpopulations in the rat basolateral amygdala
Brain Res.
Localization of dopamine D3 receptor mRNA mRNA in the rat brain using in situ hybridization histochemistry: comparison with dopamine D2 receptor mRNA
Brain Res.
A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats
Pharmacol. Biochem. Behav.
Characterization of dopamine autoreceptors in the amygdala: a fast cyclic voltammetric study in vitro
Neurosci. Lett.
Dopamine receptors in human brain: autoradiographic distribution of D2 sites
Neuroscience
Ascending projections of presumed dopamine-containing neurons in the ventral tegmentum of the rat as demonstrated by horseradish peroxidase
Neuroscience
Selective activation of mesoamygdaloid dopamine neurons by conditioned stress: attenuation by diazepam
Brain Res.
Dopamine receptors in the anterior insular cortex modulate long-term nociception in the rat
Eur. J. Pain
Dopamine receptors in human brain: autoradiographic distribution of D1 sites
Neuroscience
Anxiety and affective style: role of prefrontal cortex and amygdala
Biol. Psychiatry
The role of the amygdala in fear-potentiated startle: implications for animal models of anxiety
Trends Pharmacol. Sci.
Fear-potentiated startle: a neural and pharmacological analysis
Behav. Brain Res.
The D1 dopamine receptor in the rat brain: quantitative autoradiographic localization using an iodinated ligand
Neuroscience
Defensive burying in rodents: ethology, neurobiology and psychopharmacology
Eur. J. Pharmacol.
Electrophysiological identification of mesencephalic ventromedial tegmental (VMT) neurons projecting to the frontal cortex, septum and nucleus accumbens
Brain Res.
Amygdala
Footshock and conditioned stress increase 3,4-dihydroxyphenylacetic acid (DOPAC) in the ventral tegmental area but not substantia nigra
Brain Res.
Autoradiographic distribution of the D1 agonist [3H]SKF 38393, in the rat brain and spinal cord. Comparison with the distribution of D2 dopamine receptors
Neuroscience
Distribution of putative neurotransmitters in the neocortex
Neuroscience
The effects of intra-cerebral drug infusions on animals’ unconditioned fear reactions: a systematic review
Prog. Neuro-Psychopharmacol. Biol. Psychol.
A review of 25 years of the social interaction test
Eur. J. Pharmacol.
Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat
Brain Res.
Morphological and functional aspects of central monoamine neurons
Int. Rev. Neurobiol.
The dopamine D1 receptor-rich main and paracapsular intercalated nerve cell groups of the rat amygdala: relationship to the dopamine innervation
Neuroscience
From the Golgi-Cajal mapping to the transmitter-based characterization of the neural networks leading to two modes of brain communication: wiring and volume transmission
Brain Res. Rev.
Receptor–receptor interactions within receptor mosaics. Impact on neuropsychopharmacology
Brain Res. Rev.
Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex
J. Neurochem.
Dopamine “autoreceptors”. Pharmacological characterization by microiontophoretic single cell recording studies
Naunyn Schmiedebergs Arch. Pharmac.
Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons
Pharmacol. Rev.
A Boolean network modelling of receptor mosaics relevance of topology and cooperativity
J. Neural Transm.
Anatomical organization of the primate amygdaloid complex
Ascending monoamine neurons to the telencephalon and diencephalon
Acta Physiol. Scand.
Comparative single and double immunolabelling with antisera against catecholamine biosynthetic enzymes: criteria for the identification of dopaminergic, noradrenergic and adrenergic structures in selected rat brain areas
Histochemistry
Ultrastructural features of tyrosine-hydroxylase-immunoreactive afferents and their targets in the rat amygdala
Cell Tissue Res.
The effects of intra-amygdaloid injections of 6-hydroxy-dopamine on avoidance responding in rats
Br. J. Pharmacol.
The amygdalar circuit that acquires taste aversion memory differs from the circuit that extinguishes it
Eur. J. Neurosci.
Brain mediation of active and passive emotional coping
Prog. Brain Res.
Mesocortical dopamine neurons: lack of autoreceptors modulating dopamine synthesis
Mol. Pharmacol.
Cited by (216)
The role of lateral hypothalamic nucleus in mediating locomotive behaviors in pigeons (Columba livia)
2024, Behavioural Brain ResearchFood-derived protein hydrolysates and peptides: anxiolytic and antidepressant activities, characteristics, and mechanisms
2024, Food Science and Human WellnessTributyltin causes generational neurodevelopmental toxicity and the protective effect of folic acid in zebrafish
2024, Journal of Environmental Sciences (China)Heterogeneity of Response to Methylphenidate in Apathetic Patients in the ADMET 2 Trial
2023, American Journal of Geriatric PsychiatryShort daylight photoperiod alleviated alarm substance-stimulated fear response of zebrafish
2023, General and Comparative Endocrinology