Dopamine depletion effects

COMMENT I would dispute it within the dopamine system itself And I would dispute it about Parkinson s disease. I think that if you did a proper neuropsychological exam that you would pick up even smaller depletion effects. I think if you are looking for an overt complete terminal Parkinson situation, yes, you need a 99 percent depletion. But part of the problem is that the Parkinson situation involves not only the nigrostriatal system but also the mesolimbic dopamine system. There are plenty of studies in rats, and it is very easy to produce a Parkinsonian rat with a very discrete... 

Leng A., Mura A., Hengerer B., Feldon J., Ferger B. (2004). Effects of blocking the dopamine biosynthesis and of neurotoxic dopamine depletion with l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) on voluntary wheel running in mice. Ilehav. Brain Res. 154, 375-83. 

Symptomatic treatment. The chorea of Huntington s disease responds (partially) to treatment with neuroleptics, which, through blockade of D2 receptors, may help to increase basal ganglia output to more normal levels. Dopamine-depleting agents, such as reserpine or tetra-benazine have also been used. At best, these agents are only moderately effective and they should only be used if the chorea truly interferes with activities of daily living or produces social embarrassment. Neuroleptics and... 

Dopamine depleting agents. Reserpine, a natural alkaloid that blocks vesicular transport of monoamines, depletes stored monoamines, including DA. DA depletion is associated with the emergence of parkinsonism. This effect of reserpine was among the first clues that PD is the result of DA deficiency (see above). Generally, the parkinsonism resulting from reserpine is reversible. 

A recent study further supported the involvement of dopamine in the mechanism of antidepressants [82]. In this study, the antidepressant-like effect of citalo-pram, paroxetine, desipramine and imipramine in the mouse forced swim test (FST) was compared with and without dopamine depletion. It was found that lesioning with 6-OHDA did not affect the response of mice to desipramine and imipramine, whereas dopamine depletion abolished the antidepressant-like effect of citalopram and paroxetine. These results suggest that the antidepressant-like effect of SSRIs in the FST requires the activation of dopaminergic pathways. 

Gerrits MA, Van Ree JM (1996) Effect of nucleus accumbens dopamine depletion on motivational aspects involved in initiation of cocaine and heroin self-administration in rats. Brain Res 713 114-124... 

The most troublesome untoward effects of treatment with reserpine involve the CNS. Sedation and depression are the most common, although nightmares and thoughts of suicide also occur. Reserpine treatment, therefore, is contraindicated in patients with a history of severe depression. The occasional report of re-serpine-induced extrapyramidal symptoms, which are similar to those seen in patients with Parkinson s disease, is believed to be a result of dopamine depletion from neurons in the CNS. 

High doses of reserpine characteristically produce sedation, lassitude, nightmares, and severe mental depression occasionally, these occur even in patients receiving low doses (0.25 mg/d). Much less frequently, ordinary low doses of reserpine produce extrapyramidal effects resembling Parkinson s disease, probably as a result of dopamine depletion in the corpus striatum. Although these central effects are uncommon, it should be stressed that they may occur at any time, even after months of uneventful treatment. Patients with a history of mental depression should not receive reserpine, and the drug should be stopped if depression appears. 

Stevens KE, Luthman J, Lindqvist E, Johnson RG, Rose GM. 1996b. Effects of neonatal dopamine depletion on sensory inhibition in the rat. Pharmacol Biochem Behav 53 817-823. 

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Baunez C, Robbins TW (1999) Effects of dopamine depletion of the dorsal striatum and further interaction with subthalamic nucleus lesions in an attentional task in the rat. Neuroscience 92 1343-1356. 

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Bruno JP, Snyder AM, Strieker EM (1984) Effect of dopamine-depleting brain lesions on suckling and weaning in rats. Behav Neurosci 95 156 161. 

Carli M, Jones GH, Robbins TW (1989) Effects of unilateral dorsal and ventral striatal dopamine depletion on visual neglect in the rat a neural and behavioural analysis. Neuroscience 29 309-327. 

Hollerman JR, Grace AA (1990) The effects of dopamine-depleting brain lesions on the electrophysiological activity of rat substantia nigra dopamine neurons. Brain Res 533 203-212. 

Johnson SK, Medina D, Wagner GC (1992) The effects of deprenyl on methamphetamine-induced dopamine depletions. J Neur Trans Gen 59 123-127. 

Moy SS, Criswell HE, Breese GR (1997) Differential effects of bilateral dopamine depletion in neonatal and adult rats. Neurosci Biobehav Rev 27 425 135. 

Caine SB, Koob GF (1994) Effects of mesolimbic dopamine depletion on responding maintained by cocaine and food. J Exp Anal Behav 61 (2) 213—221. 

Collins P, Wilkinson LS, Everitt BJ, Robbins TW, Roberts AC (2000) The effect of dopamine depletion from the caudate nucleus of the common marmoset (callithrix jacchus) on tests of prefrontal cognitive function. 

Racke K, Meuresch J, Trapp B, Muscholl E (1986) Modulation by fenoldopam (SKF 82526) and bromocriptine of the electrically evoked release of vasopressin from the rat neurohypophysis. Effects of dopamine depletion. Arch Pharmacol 332 332-337. 

As in AD, knowdedge of the neurotransmitter deficiency underlying PD, in this case dopamine, has been the basis for the development of therapy. Early studies show ed that cerebral dopamine was concentrated in the shiatum and that levodopa, the precursor to dopamine, could reverse the akinetic effects of the dopamine-depleting agent reserpine in experimental animals (Carlsson et al., 1957, 1958). Eventually, the identification of shiatal dopamine depletion as a key neurochemical finding in parkinsonian brains lead to heatment wdth levodopa in humans and to the subsequent advent of compounds that mimic the effects of dopamine or prolong its action (Table 39.2). 

While the dopamine depleted striatum provides a good model for study of the selective effects of D1 and D2 receptor stimulation these effects are abnormal in the sense that the pharmacologic treatments that alter gene regulation in the lesioned striatum are not paralleled in the unlesioned striatum. These differences in effect are not due to a redistribution of the receptor subtypes, as the segregated localization of the D1 and D2 receptor subtypes to striatonigral and striatopallidal neurons occurs in both the lesioned... 

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