Caudate

Acetylcholine is a neurotransmitter at the neuromuscular junction in autonomic ganglia and at postgangHonic parasympathetic nerve endings (see Neuroregulators). In the CNS, the motor-neuron collaterals to the Renshaw cells are cholinergic (43). In the rat brain, acetylcholine occurs in high concentrations in the interpeduncular and caudate nuclei (44). The LD q (subcutaneous) of the chloride in rats is 250 mg/kg. 

Youngren KD, Inglis FM, Pivirotto PJ et al (1999) Clozapine preferentially increases dopamine release in the rhesus monkey prefrontal cortex compared with the caudate nucleus. Neuropsychopharmacology 20 403-12... 

Basal ganglia are a group of subcortical nuclei which are essential for the coordination of movements (so-called extrapyramidal system). They include the caudate nucleus, putamen, globus pallidus, and lenti-form nucleus. Damage of the basal ganglia results in involuntary movements, as are observed in Parkinson s disease and Huntington s chorea. 

Dementia with Lewy bodies (DLB) is considered the second most common cause of dementia after AD. The disorder is characterized by progressive fluctuating cognitive impairment, visual hallucinations and motor features of Parkinsonism. Neocoitical cholinergic activity is more severely depleted in DLB than in AD, and DLB also affects the caudate nucleus, the thalamus and the brain stem. Tolerability of ChEI in DLB appears similar to AD, with some gastrointestinal effects and muscle cramps. 

Highest concentrations of MOPs are found in the thalamus, caudate, neocortex in the brain, but the receptors are also present in gastrointestinal tract, immune cells, and other peripheral tissues. 

A high concentration of DOPs is found in the olfactory bulb, the neocortex, caudate putamen, and in the spinal cord, but they are also present in the gastrointestinal tract and other peripheral tissues. The functional roles of DOP are less clearly established than for MOP they may have a role in analgesia, gastrointestinal motility, mood and behaviour as well as in cardiovascular regulation [2]. 

Motor stereotypy Dorsal striatum (i.e., caudate putamen)... 

Localization CNS Hippocampus (CA1, CA3, DG), septum, amygdala, raphe nuclei CNS Striatum, hippocampus (CA1), substantia nigra, globus pallidus, superior colliculi, spinal cord, raphe nuclei CNS like 5-HT1B but at lower densities. CNS Caudate putamen, parietal cortex, fronto-parietal motor cortex, olfactory tubercle, amygdala CNS Cortex, Thalamus, olfactory bulb (rat), claustrum (g-pig), hippocampus (CA3), spinal cord. 

Localisation CA/S Hippocampus (CA1, CA3, DG), cortex, cerebellum (granular layer), olfactory bulb, habenula, spinal cord CA/S Caudate putamen, olfactory tubercle, nucleus accumbens, cortex, hippocampus (CA1, CA3, DG) CA/S Hippocampus (CA1, CA2), hypothalamus, thalamus, superior colliculus, raphe nuclei... 

Fuxe K, Andersson K, Nilsen OG, et al Toluene and telencephalic dopamine selective reduction of amine mrnover in discrete DA nerve terminal systems of the anterior caudate nucleus by low concentrations of toluene. Toxicol Lett 12 115—123,1982 Cause EM, Mendez V, Geller I Exploratory smdies of a rodent model for inhalant abuse. Neurobehav Toxicol Teratol 7 143—148, 1985 Gentry JR, Hill C, Malcolm R New anticonvulsants a review of applications for the management of substance abuse disorders. Ann Clin Psychiatry 14 233—245, 2002 Gerasimov MR, Ferrieri RA, Schiffer WK, et al Smdy of brain uptake and biodistribution of [llCjtoluene in non-human primates and mice. Life Sci 70 2811 — 2828, 2002... 

Hillefors-Berglund M, Liu Y, von Euler G Persistent, specific and dose-dependent effects of toluene exposure on dopamine D2 agonist binding in the rat caudate-putamen. Toxicology 77 223-232, 1993... 

Fig. 8.1 Rostrocaudal neuroanatomical distribution of CCR5-immunoreactivity in the telencephalon, diencephalon and mesencephalon using a CCR5 antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA). Regions corresponding to pictures are depicted in coronal diagrams taken from the Paxinos and Watson (1998). (a, b) M Motor cortex, (c, d) CPu caudate putamen (striatum), (e,t)SID substantia innominata dorsal part, (g, h) GP globus pallidus, (i, j)Me medial amygdaloid...

Of course, while the identification of these distinct systems may be useful there are many neural pathways that would not fit easily into one of them. Thus some inhibitory pathways, such as that from the caudate nucleus to substantia nigra, utilising GABA, are not intrinsic neurons. The dopamine pathway from the substantia nigra to striatum may start from a small nucleus but unlike other monoamine pathways it shows little ramification beyond its influence on the striatum. The object of the above classification is not to fit all neural pathways and mechanisms into a restricted number of functional categories but again to demonstrate that there are different forms of neurotransmission. 

ACh is widely distributed throughout the brain and parts of the spinal cord (ventral horn and dorsal columns). Whole brain concentrations of lOnmolg" tissue have been reported with highest concentrations in the interpeduncular, caudate and dorsal raphe nuclei. Turnover figures of 0.15-2.0 nmol g min vary with the area studied and the method of measurement, e.g. synthesis of labelled ACh from [ " C]-choline uptake or rundown of ACh after inhibition of choline uptake by hemicholinium. They are all sufficiently high, however, to suggest that in the absence of synthesis depletion could occur within minutes. 

Figure 7.1 Dopamine neuronal pathways. AMYG, amygdala CN, caudate nucleus MFB, medial forebrain bundle NcA, nucleus accumbers OT, olfactory tubercle PUT, putamen SN, substantia nigra. For full details see text and Moore and Bloom (1978) and Lindvall and Bjorkland (1978)...

Certainly the activity of tyrosine hydroxylase is greater in the DA neurons of the substantia nigra (17.5 nmol dopa synthesised/mg protein/h) than in the NA neurons of the locus coeruleus (4-5), as is the turnover of the amine itself (1.7 pg/h) compared with that of NA (1.0) (see Bacopoulus and Bhatnager 1977). In the caudate nucleus and nucleus accumbens the turnover of DA is even higher at 7.4 and 2-6 pg/g/h respectively. 

D3 Much less abundant than D2. Mainly in limbic regions (nucleus accumbens and olfactory tubercle) but also in hypothalamus. Some in caudate and cortex and also expressed on DA neurons in substantia nigra, presumably as autoreceptors. No effect on adenylate cyclase but inhibits Ca + entry (autoreceptor role). High affinity for DA (Ali 25nM). 

Figure 7.7 Dopamine-induced rotation in the rat in which one (left) nigrostriatal dopamine pathway from the substantia nigra (SN) to the caudate putamen (CP) has been lesioned by a prior injection (14 days) of 6-hydroxydopamine. Amphetamine, an indirectly acting amine, releases DA and so can only act on the right side. Since the animal moves away from the dominating active side it induces ipsilateral rotation (i.e. towards the lesioned side). By contrast, the development of postS5maptic supersensitivity to DA on the lesioned side ensures that apomorphine, a directly acting agonist, is actually more active on that side and so the animal turns away from it (contralateral rotation)...

Hu, XT and Wang, RY (1988) Comparison of effects of Dj and D2 dopamine receptor agonists on neurons in the rat caudate putamen an electrophysiological study. J. Neurosci. 8 4340-4348. 

Kebabian, JW and Caine, DB (1979) Multiple receptors for dopamine. Nature 277 93-96. Kitai, ST, Sugimori, M and Kocsis, JC (1976) Excitatory nature of dopamine in the nigro-caudate pathway. Exp. Brain Res. 24 351-363. 

Since these neurons form the dopaminergic nigrostriatial tract (Fig. 7.1) it is not surprising that PD patients also show a loss of striatal DA. This was first detected in post-mortem studies in 1960 by Hornykiewicz and numerous studies since have shown that not only is PD associated with and presumably caused by a loss of striatal DA, but at death that loss actually reaches more than 80%. Within the striatum DA loss is greater in the putamen which has predominantly motor links with the cortex than in the caudate mucleus with its connections to cortical association areas. 

In order to understand how the symptoms of PD could arise from a loss of striatal DA and what can be done to replace it and treat PD, it is necessary to know something of basal ganglia circuitry and the role of DA in it. The scheme to be outlined should, however, be regarded as a working template rather than fully proven fact but there is much evidence for it (Fig. 15.2). Certainly the striatum, i.e. the putamen and caudate nucleus, is accepted as the main receiving area in motor circuits. Information coming to... 

Jolkkonen, J, Jenner, P and Marsden, CD (1995) L-Dopa reverses altered gene expression of substance P but not enkephalin in the caudate-putamen of common marmosets treated with MPTP. Brain Res. Mol. Brain Res. 32 297-307. 

It could not be anticipated that the extension of the alpha-methyl of MDMA to an alpha-ethyl would also attenuate the effects of the compound on dopaminergic pathways in the brain. In contrast to MDMA, MBDB has no significant effect either on inhibition of uptake of dopamine into striatal synaptosomes (Steele et al. 1987) or on release of dopamine from caudate... 

Seiden, L.S., and Vosmer. G. Formation of 6-hydroxydopamine in caudate nucleus of the rat brain after a single large dose of methylamphetamine. Pharmacol Biochem Behav 21 29-31, 1984. 

Hull, C.D. Bemardi, G. Price, D.D. and Buchwald, N.A. Intracellular responses of caudate neurons to temporally and spatially combined stimuli. Exp Neurol 38 324-336, 1973. 

Kemp, J.M., and Powell, T.P.S. The structure of the caudate nucleus of the car Light and electron microscopy. Philos Trans R Soc Bond [Biol] 262 383-401, 1971. 

Wagner, G.C. Ricaurte, G.A. Johanson, C.E. Schuster, C.R. and Seiden, L.S. Amphetamine induces depletion of dopamine and loss of dopamine uptake sites in caudate. Neurology 20 547-550. 1980. 

As shown in table 2 and figure 9, marked decreases in serotonin uptake sites were observed following MDMA administration in all regions of eaudate putamen, olfactory tubercle, endopiriform nueleus, islands of Calleja, and nucleus aeeumbens. Within the caudate putamen, some time-dependent... 

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