Nucleus accumbens, dopamine projections

O Virtually all abused substances appear to activate the same brain reward pathway. Key components of the reward pathway are the dopamine (DA) mesocorticolimbic system that projects from the ventral tegmental area (VTA) and the nucleus accumbens (NA) to the prefrontal cortex, the amygdala, and the olfactory tubercle (Figs. 33-3 and 33-4).5 Animal studies... 

Heimer L, Zahm DS, ChurchUl L, Kalivas PW, Wohltman C (1991) Specificity in the projection patterns of accumbal core and medial shell in the rat. Neuroscience 41 89-125 Hemby SE, No C, Koves TR, Smith JE, Dworkin SI (1997) Differences in extracellular dopamine concentration in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat. Psychopharmacology 133 7-16 Hildebrand BE, Nomikos GG, Hertel P, Sclrilstrom B, Svensson TH (1998) Reduced dopamine output in the nucleus accumbens but not the prefrontal cortex in rats displaying mecamylamine-precipitated nicotine withdrawal syndrome. Brain Res 779 214-225 Ikemoto S (2003) Involvement of the olfactory tubercle in cocaine reward intracranial selfadministration studies. J Neurosd 23 9305-9311... 

Balfour DJ (2002) Neuroplasticity within the mesoaccumbens dopamine system and its role in tobacco Dependence, Curr Drug Targets CNS Neurol Disord 1 413-21 Balfour DJ (2004) The neurobiology of tobacco dependence a preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res 6 899-912 Barik J, Wonnacott S (2006) Indirect modulation by alpha7 nicotinic acetylcholine receptors of noradrenaline release in rat hippocampal slices interaction with glutamate and GABA systems and effect of nicotine withdrawal. Mol Pharmacol 69 618-628... 

The long length fibres link the ventral tegmental and substantia nigra dopamine-containing cells with the neostriatum (mainly the caudate and the putamen), the limbic cortex (the medial prefrontal, cingulate and entorhinal areas) and with limbic structures such as the septum, nucleus accumbens, amygdaloid complex and piriform cortex. These projections are... 

Willner (1995) provides evidence from many sources that increases or decreases of dopaminergic activity in the mesolimbic system may underpin the pathophysiology of mania and depression respectively. A key area involved may be the subgenual prefrontal cortex which receives extensive reciprocal dopaminergic projections from the ventral tegmental area and substantia nigra and influences dopamine release in the nucleus accumbens (Drevets et al., 1997 see Chapter 16). 

Jeffrey W. Dailey, at the University of Cambridge in the United Kingdom, along with his colleagues, studied rat behavior in combination with chemical analyses and PET. (PET works with laboratory animals as well as with humans.) Of particular interest is an area of the brain called the nucleus accumbens, a region deep in the brain that receives a projection from neurons that use dopamine as a neurotransmitter. Drug use significantly increases this transmission. 

The mesolimbic dopamine pathway projects from dopaminergic cell bodies in the ventral tegmental area of the brainstem to axon terminals in limbic areas of the brain, such as the nucleus accumbens (Fig. 10—8). This pathway is thought to have an important role in emotional behaviors, especially auditory hallucinations but also delusions and thought disorder (Fig. 10—9)-... 

A key effect of addictive psychotropic drugs is to increase the extracellular concentration of dopamine in the nucleus accumbens. Ethanol does this in part by direct excitation of the mesolimbic dopamine neurons projecting to the accumbens (Koyama et al. 2007). However, studies in alcohol-preferring rats, animals which tend to develop alcohol dependence, have indicated an additional component a reduction of presynaptic D2 autoreceptor function (Engleman et al. 2003 Thielen et al. 2004). 

Pinto A, Jankowski M, Sesack SR (2003) Projections from the paraventricular nucleus of the thalamus to the rat prefrontal cortex and nucleus accumbens shell ultrastructural characteristics and spatial relationships with dopamine afferents. J Comp Neurol 459 142-155. 

Fig. 2. A. Forebrain dopamine projection system in rodents and primates. The nigrostriatal pathway projects from the A8 and A9 groups of the substantia nigra (SN) via the medial forebrain bundle (mfb) to the neostriatum (NS). The mesocorticolimbic pathway projects from the more medially located A10 cell group of the ventral tegmental area (VTA) to the nucleus accumbens (NAcc) and olfactory tubercle (OT) of the ventral striatum (VS) and limbic forebrain areas including prefrontal cortex (Ctx), septum (Se) and amygdala (A). B. Striatal projection areas in the rodent brain are divided into the more dorsal neostriatum, and ventral striatum. C. In the primate brain, including human and illustrated for the marmoset, the neostriatum is divided by the fibers of the internal capsule into caudate nucleus (CN) and putamen (Pu). Correspondingly, the neostriatum of rats is sometimes designated the caudate-putamen (CPu) complex.

MPTP toxicity in primates. Following peripheral administration, MPTP induces a similar Parkinsonian syndrome in monkeys, and pathological examination reveals a profound loss of neurones in the substantia nigra, the appearance of degenerating dopamine terminals in the striatum and a loss of dopamine and HVA from the striatum (Burns et al., 1983 Forno et al., 1984 Langston et al., 1984). By contrast, locus coeruleus, nucleus accumbens and olfactory tubercle were less depleted in the early studies, but have been found to be affected, along with projections to frontal cortex as well as the striatum, in other reports dependent upon different parameters for administration of the toxin (Elsworth et al., 1990 Hornykiewicz and Pifl, 1994). 

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