Nucleus accumbens presynaptic

D2 Mostly in striatum, nucleus accumbens and olfactory tubercle but also on neuron cell bodies in substantia nigra and ventral tegmentum where they are the autoreceptors for locally (dendritic) released DA. The loss of specific D2 antagonist binding in the striatum after lesions of the afferent nigro-striatal tract indicates their presynaptic autoreceptor role on terminals there. Other lesion studies have also established D2 receptors on other inputs such as the cortico striatal tract. 

So far, little is known about this novel 5-HTid receptor but, in the rat and human, its mRNA is found, albeit in low concentrations, in the basal ganglia, nucleus accumbens, hippocampus, frontal cortex and Raphe nuclei. It is negatively coupled to adenylyl cyclase and is possibly located presynaptically, on both the 5-HT neuronal cell body and terminals, but this has yet to be confirmed. 

The neuroehemical sites for psyehomotor stimulant reward are likely to be the presynaptic dopamine terminals located in the region of the nucleus aeeumbens, frontal cortex, and other forebrain structures that originate in the ventral tegmental area. Note, however, that intraeranial self-administration of eoeaine is elicited from the frontal cortex, but not from the nucleus aeeumbens (Goeders and Smith 1983). Thus, eoneomitant activation of structures other than the nucleus accumbens may be an important part of the circuitry involved in initiation of cocaine intravenous self-administration, as has been hypothesized for the opiates (Smith and Lane 1983 Smith et al. 1982). 

Chen, J., Paredes, W., Li, J., Smith, D., Lowinson, J., and Gardner, E.L., In vivo brain microdialysis studies of A9-tetrahydrocannabinol on presynaptic dopamine efflux in nucleus accumbens of the Lewis rat, Psychopharmacology, 102, 156, 1990. 

Louilot, A., Le Moal, M., and Simon, H., Presynaptic control of dopamine metabolism in the nucleus accumbens. Lack of effect of buspirone as demonstrated using in vivo voltammetry, Life Sci., 40, 2017, 1987. 

Chen J, Paredes W, Li J, Lowinson J and Gardner EL (1990a). A9-tetrahydrocannabinol produces naloxone-blockade enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology, 102, 156-162. 

The Dj-dopaminergic receptor decreases cAMP production by inhibiting dopamine-sensitive adenylyl cyclase and opens channels but can also block Ca++ channels. It is located both presynaptically and postsyn-aptically on neurons in the caudate putamen, nucleus accumbens, and olfactory tubercle. Another member of this family is the Dj-receptor, which also decreases... 

Atomoxetine is a selective inhibitor of norepinephrine presynaptic reuptake transporters that has been shown to increase extracellular norepinephrine and dopamine concentrations in the prefrontal cortex in rats (Bymaster et al. 2002), which may account for its clinical efficacy in the treatment of ADHD symptomatology. However, atomoxetine does not appear to affect dopamine levels in the striatum or nucleus accumbens and consequently is not thought to carry the abuse potential associated with stimulant medications. 

Mu receptors are almost always located proximally, on the presynaptic side of the synapse. The periaqueductal gray is the region containing the most mu receptors, but they are also found in the superficial dorsal hom of the spinal cord, the external plexiform layer of the olfactory bulb, the nucleus accumbens (an area deeply implicated in the process of addiction), in some parts of the cerebral cortex, and in some of the nuclei of the amygdala. Mu receptors avidly bind enkephalins and beta-endorphin, but they have a low affinity for dynorphins (primarily a kappa receptor agonist).6... 

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). 

Mizuno T, Schmauss C, Rayport S (2007) Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens. BMC Neurosci 8 8-23... 

Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Aihara H (1988b) Serotonin-2 receptor-mediated regulation of release of acetylcholine by minaprine in cholinergic nerve terminal of hippocampus of rat. Neuropharmacology 27 603-9 Muramatsu M, Lapiz MD, Tanaka E, Grenhoff J (1998) Serotonin inhibits synaptic glutamate currents in rat nucleus accumbens neurons via presynaptic 5-HTjb receptors. Eur J Neurosci 10 2371-9... 

Nicola SM, Kombian SB, Malenka RC (1996) Psychostimulants depress excitatory synaptic transmission in the nucleus accumbens via presynaptic Dj-like dopamine receptors. J Neurosci 16 1591-604... 

Umemiya M, Berger AJ (1995) Presynaptic inhibition by serotonin of glycinergic inhibitory synaptic currents in the rat brain stem. J Neurophysiol 73 1192-1201 Usiello A, Baik JH, Rouge-Pont F, Picetti R, Dierich A, LeMeur M, Piazza PV, Borrelli E (2000) Distinct functions of the two isoforms of dopamine D2 receptors. Nature 408 199-203 Vanderschuren LJ, Wardeh G, De Vries TJ, Mulder AH, Schoffelmeer AN (1999) Opposing role of dopamine Di and D2 receptors in modulation of rat nucleus accumbens noradrenaline release. J Neurosci 19 4123-31... 

Geldwert D, Norris JM, Feldman IG, Schulman JJ, Joyce MP, et al. 2006. Dopamine presynaptically and heterogeneously modulates nucleus accumbens medium-spiny neuron GABA synapses in vitro. BMC Neurosci 7 53. 

Svingos AL, Periasamy S, Pickel VM (2000) Presynaptic dopamine D4 receptor localization in the rat nucleus accumbens shell. Synapse 36 222-232. 

Wong AC, Shetreat ME, Clarke JO, Rayport S (1999) D1 and D2-like dopamine receptors are co-localized on the presynaptic varicosities of striatal and nucleus accumbens neurons in vitro. Neurosci 89 221-233. 

---