ISSN:
1432-2072
Keywords:
Noradrenaline
;
3-Methoxy-4-Hydroxy-phenylethyleneglycol
;
Cyclic AMP
;
Locus coeruleus
;
Neuroleptic treatment
;
Clozapine
;
Haloperidol
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The influence of single and repeated neuroleptic treatment on noradrenaline (NA) metabolism in two areas of the central nervous system with different neuronal organizations (forebrain and spinal cord) was studied. The doses of the neuroleptics studied were chosen because of their maximum effects on turnover of dopamine in various brain areas. The endogenous levels of 3-methoxy-4-hydroxy-phenylethyleneglycol (MOPEG) in the forebrain and spinal cord of the rat were markedly increased by single intraperitoneal doses of clozapine (15 mg/kg), haloperidol (1.0 mg/kg) or chlorpromazine (2.0 mg/kg). The levels of noradrenaline (NA) in the hippocampus were decreased by a single dose of clozapine and haloperidol. Fluphenazine (0.1 mg/kg) and sulpiride (40 mg/kg) caused only slight increases of MOPEG in the forebrain and none in the spinal cord. Following repeated treatment with either clozapine or haloperidol tolerance to the stimulatory effects on NA turnover developed more rapidly in the spinal cord than in the forebrain (within 4 and 15 days respectively). After 4 days of repeated treatment the initial decrease in hippocampal NA levels had disappeared. Unilateral electrical stimulation of the locus coeruleus (LC) after a single dose of either clozapine or haloperidol induced smaller reductions of hippocampal NA (ipsilateral versus contralateral) than in saline treated control animals. In subchronically clozapine or haloperidol treated rats, LC-stimulation induced an ipsilateral decrease of NA similar to that in controls. The levels of MOPEG after LC-stimulation were elevated compared to untreated stimulated rats both in the ipsilateral and contralateral forebrain. Neither single nor repeated treatment with clozapine or haloperidol altered basal cyclic AMP levels or inhibited the cyclic AMP response to LC-stimulation. This study is evidence: (1) that neuroleptics decrease NA by release of the amine from a rapidly releasable pool (2) that even when the influence of subchronic neuroleptic treatment on cerebral NA metabolism has ceased, such treatment has a lasting influence on NA-neurons (3) that in vivo the formation of cyclic AMP is not influenced by neuroleptic treatment.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00427880
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