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Key Event Title
Dopamine release in the brain, decreased
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Inhibition of CYP7B leads to decreased locomotor activity||KeyEvent||Brendan Ferreri-Hanberry (send email)||Not under active development|
|Inhibition of CYP7B activity leads to decreased sexual behavior||KeyEvent||Arthur Author (send email)||Not under active development|
|All life stages|
Key Event Description
Dopamine is a monoamine, catecholaminergic neurotransmitter synthesized in the brain and the kidney from precursor L-DOPA (Carlsson et al., 1957). It is synthesized in neuron cells, stored in vesicules nearby the synaps, and is released into the synaptic cleft after excitation of the neuron. Once released, it can bind D1-like or D2-like G protein receptor which have different effects (Stoof and Kebabia, 1984; Vallender et al., 2010).
It is conserved among vertabrates and regulates neural activity, behavior and gene expression. The main impacts are related to voluntary movement, feeding, and reward.
In birds, fish, and other vertebrates, dopaminergic neurons located in mesencephalic region (VTA, SN) project to the telencephalon, a region of the brain rich in D1 and D2 receptors (Hara et al., 2007; Ball et al., 1995; Levens et al., 2000).
How It Is Measured or Detected
To measure the ability of a molecule to stimulate dopamine release, brain can be incubated in physiological saline in presence of a presumptive activator (e.g. 7α-hydroxypregnenolone, a neurosteroid) and dopamine concentration in saline is measured by HPLC-ECD (Matsunaga et al., 2004).
To measure the concentration of dopamine in the brain in vivo, freshly collected brain can be homogenized and dopamine concentration can be analyzed using HPLC-ECD (ECD-300, Eicom).
Domain of Applicability
Dopamine is used as a neurotransmitter in multicellular animals (Barron et al., 2010). Across a wide range of vertebrates, dopamine has an "activating" effect on behavior-switching and response selection, comparable to its effect in mammals.
Barron, A.B., Sovik, E., and Cornish, J.L. (2010). The roles of dopamine and related compounds in reward-seeking behavior across animal phyla. Front Behav Neurosci 4, 163.
Carlsson, A., Lindqvist, M., and Magnusson, T. (1957). 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 180, 1200.
Matsunaga, M., Ukena, K., Baulieu, E.E., and Tsutsui, K. (2004). 7alpha-Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system. Proc Natl Acad Sci U S A 101, 17282-17287.
Stoof, J.C., and Kebabian, J.W. (1984). Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sci 35, 2281-2296.
Vallender, E.J., Xie, Z., Westmoreland, S.V., and Miller, G.M. (2010). Functional evolution of the trace amine associated receptors in mammals and the loss of TAAR1 in dogs. BMC Evol Biol 10, 51.