.. Figure 2. Neurotransmission via a G protein-coupled receptor (GPCR): binding of the neurotransmitter to the receptor initiates a cascade of intracellular events that drive the activity of the neuron or cell. The G-protein complex, consisting of subunits α, … Various experiments

have shown that during stress, noradrenergic and adrenergic neurons release more noradrenaline and adrenaline, respectively, and that the turnover of these neurotransmitters is accelerated so that their concentrations and/or amounts of their metabolites fluctuate in relation to the intensity and duration Inhibitors,research,lifescience,medical of the stressor.7 -10 Acute stress induces only a transient rise in noradrenaline levels, but chronic stress with recurrent environmental challenges can lead to repetitive increases in concentration. As a consequence, adrenoceptors on the surface of the target neurons Inhibitors,research,lifescience,medical are bombarded with noradrenaline, leading to a reduction in adrenoceptor numbers (receptor downregulation).11 On the other hand, low concentrations of noradrenaline induce adrenoceptor upregulation.12 Changes in α2-ARS alter the activity of neurons The most studied adrenergic receptors, with respect to regulation in chronic stress, are the α2-adrenoceptors (α2-ARs), of which three subtypes are known (A, R, and C).13 Because of their widespread distribution Inhibitors,research,lifescience,medical in the brain, α2-ARs are diversely involved in mediating the analgesic

and sedative effects of agonists such as dexmedetomidine14 and in modulating the baroreceptor reflex.15 The involvement of α2-ARs in the regulation of attention is suggested by the finding that mcthylphcnidate (the nonamphetamine stimulant Inhibitors,research,lifescience,medical used to treat children with attention-deficit hyperactivity disorder) affects neuronal activity in the LC.16 Administration of the antagonist yohimbine (a sympatholytic drug that is used to treat impotence) increases firing of the LC neurons, resulting in anxiety-like behavior in rats and monkeys.17 Brain α2-AR changes have been observed in depressed patients (see below). The α2A-AR autoreccptor in LC noradrenergic neurons, regulates noradrenaline

release via a negative Inhibitors,research,lifescience,medical feedback loop.14-18 Expression of this autoreceptor is reduced soon after the onset of stress (see below). In addition, α2A-AR is also expressed in neurons that release the excitatory neurotransmitter glutamate.“ In general, α2-AR stimulation leads to a transient inhibition of neuronal firing through Dacomitinib hyperpolarization that is related to the modulation of calcium and potassium channels.20,21 There is reduced intracellular formation of the http://www.selleckchem.com/products/Cisplatin.html second messenger, cAMP, which itself regulates many cellular functions including gene Ganetespib order transcription.22,23 Different forms of stress, such as immobilization or a cold environment, alter α2-AR numbers in distinct brain regions.24,25 We investigated the consequences of chronic psychosocial stress using a stress paradigm in male shrews.