+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Overflow of noradrenaline and dopamine in frontal cortex after [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] (DSP-4) treatment: in vivo microdialysis study in anaesthetized rats



Overflow of noradrenaline and dopamine in frontal cortex after [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] (DSP-4) treatment: in vivo microdialysis study in anaesthetized rats



Naunyn-Schmiedeberg's Archives of Pharmacology 355(2): 267-272



The changes in the extracellular concentration of endogenous noradrenaline and dopamine in the frontal cortex following pretreatment with noradrenergic neurotoxin DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] were studied by in vivo microdialysis in rats anaesthetized with chloral hydrate. Noradrenaline and dopamine levels in frontal cortex were detected only when the uptake inhibitor, nomifensine (10 microM) was present in dialysis fluid. Under those conditions, the Na+ channel agonist veratridine and a depolarising concentration of potassium chloride (60 mM), applied locally through the microdialysis probe, increased the overflow of noradrenaline. Tetrodotoxin had an opposite effect. These results indicate that most of the noradrenaline probably arose from exocytotic release. Noradrenaline efflux in the frontal cortex of DSP-4 pretreated rats (52 +/- 6.1 fmol/sample) did not differ significantly from that of the control animals (69 +/- 4.9 fmol/sample). Dopamine efflux was not changed either (64 +/- 9.6 and 62 +/- 3.9 fmol/sample, respectively). The alpha 2-adrenoceptor antagonist, atipamezole (3 mg/kg i.p.), increased the overflow of noradrenaline in the frontal cortex of saline-treated rats by 100%, whereas in DSP-4 treated rats the increase was only around 30%. The overflow of dopamine was not changed under the conditions described. The effect of atipamezole in DSP-4 treated rats may be of smaller magnitude due to the diminished pool of releasable noradrenaline or due to a downregulation of presynaptic alpha 2-adrenoceptors in the frontal cortex. The perfusion of 60 mM KCl at the end of the experiment unexpectedly produced equivalent increases in noradrenaline and dopamine content in dialysates of both vehicle and DSP-4 treated rats. We conclude that the uptake inhibitor, nomifensine, and atipamezole, which had a stronger effect in vehicle-treated animals, reduced the effect of KCl-stimulation and masked the true difference in changes of noradrenaline efflux. Post-mortem tissue concentrations of noradrenaline 7 days after DSP-4 administration (50 mg/kg) were significantly reduced in the frontal cortex (54%), hippocampus (62.5%) and to lesser extent in the hypothalamus (27%) as compared to vehicle-treated rats. Dopamine and 3,4-dihydroxyphenylacetic acid concentrations were not changed confirming the efficacy and selectivity of the DSP-4 lesion. These results demonstrate that one week after DSP-4 treatment the extracellular levels of noradrenaline and dopamine as assessed by in vivo microdialysis are not changed in the frontal cortex, but atipamezole-stimulated release of noradrenaline is decreased in DSP-4 treated rats.

(PDF emailed within 0-6 h: $19.90)

Accession: 046897405

Download citation: RISBibTeXText

PMID: 9050022

DOI: 10.1007/pl00004942


Related references

Overflow of noradrenaline and dopamine in frontal cortex after (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) (DSP-4) treatment: In vivo microdialysis study in anaesthetized rats. Naunyn Schmiedeberg's Archives of Pharmacology 355(2): 267-272, 1997

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine reduces intracellular calcium response to noradrenaline in rat visual cortex. Neuroscience 107(2): 209-218, 2001

Dsp 4 n 2 chloroethyl n ethyl 2 bromobenzylamine reduces endogenous noradrenaline in slices of rat cerebral cortex by stimulating its release. Society for Neuroscience Abstracts 10(2): 1190, 1984

DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) depletes noradrenaline in kitten visual cortex without altering the effects of monocular deprivation. Journal of Neuroscience 5(7): 1925-1933, 1985

Comparison of serotonin and 5-hydroxy-indolacetic acid output in frontal cortex of chloral hydrate anaesthetized and freely moving rats: An in vivo microdialysis study. Baltic Journal of Laboratory Animal Science 11(4): 213-217, 2001

An in vivo microdialysis study in the frontal cortex of freely-moving rats Effects of FG 7142 or Yohimbine on spontaneous and stress-induced changes in noradrenaline efflux. British Journal of Pharmacology 116(PROC SUPPL ): 132P, 1995

Denervation of the locus coeruleus projections by treatment with the selective neurotoxin DSP-4 [N (2-chloroethyl)-N-ethyl-2-bromobenzylamine] reduces dopamine release potential in the nucleus accumbens shell in conscious rats. Neuroscience Letters 332(2): 79-82, 2002

A microdialysis study of the effect of flurazepam on noradrenaline efflux in the frontal cortex of freely-moving rats after treatment with yohimbine. British Journal of Pharmacology 118(PROC SUPPL JULY): 76P, 1996

Dopamine overflow is increased in olfactory bulbectomized rats: an in vivo microdialysis study. Physiology & Behavior 81(1): 111-119, 2004

Synthesis of tritium labeled n 2 chloroethyl n ethyl 2 bromobenzylamine a selective noradrenaline neurotoxin. Journal of Labelled Compounds & Radiopharmaceuticals 22(11): 1143-1148, 1985

Regional differences in the regulation of dopamine and noradrenaline release in medial frontal cortex, nucleus accumbens and caudate-putamen: a microdialysis study in the rat. Brain Research 581(2): 217-228, 1992

DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine)--a useful denervation tool for central and peripheral noradrenaline neurons. European Journal of Pharmacology 72(2-3): 173-188, 1981

On the long-lasting inhibitory effect of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP 4) on the active uptake of noradrenaline. Journal of Pharmacy and Pharmacology 28(5): 458-459, 1976

Effects of the noradrenaline neurotoxin n 2 chloroethyl n ethyl 2 bromobenzylamine hydrochloride dsp4 on the blood brain barrier an experimental study in the mouse using protein tracer and density determination techniques. Acta Neuropathologica 78(1): 28-34, 1989

A partial noradrenergic lesion induced by DSP-4 increases extracellular noradrenaline concentration in rat frontal cortex: A microdialysis study in vivo. Psychopharmacology 136(3): 299-303, 1998