ISSN:
1432-1912
Schlagwort(e):
Dopamine autoreceptors
;
α-Adrenoceptor antagonists
;
Haloperidol
;
Yohimbine
;
Noradrenaline-dopamine interaction
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary The influence of various α-adrenoceptor antagonists (10 mg/kg i.p.) upon the rate of turnover of dopamine (DA) in the rat brain was investigated. Taking the levels of the DA metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as a measure of the rate of DA turnover, it was found that prazosin and phenoxybenzamine decreased, whereas piperoxane and yohimbine increased the turnover rate both in the corpus striatum and in the tuberculum olfactorium. Azapetine, phentolamine and tolazoline as well as the β-adrenoceptor antagonist propranolol were without a significant effect, whereas the DA antagonist haloperidol increased DOPAC and HVA levels and decreased the levels of DA itself. The possibility that the yohimbine-induced increase in the DA turnover rate was produced by a direct blockade of DA autoreceptors, was investigated under conditions where influences other than those elicited via DA autoreceptors are thought to be eliminated, i.e. in rats treated with reserpine or γ-butyrolactone (GBL). In rats that were pretreated with reserpine, yohimbine (10 mg/kg i.p.) was found to be ineffective in antagonizing the reduction of the accumulation of 3,4-dihydroxyphenylalanine (DOPA) following decarboxylase inhibition, that was produced by the DA agonist apomorphine (2.0 mg/kg i.p.). In rats pretreated with reserpine, yohimbine (10 mg/kg i.p.) was also ineffective in antagonizing the reduction of the DOPAC and HVA levels produced by apomorphine (2.0 mg/kg i.p.), but it was effective in antagonizing the reduction of the HVA level that was produced by the selective DA autoreceptor agonist N,N-di-n-propyl-7-hydroxy-2-aminotetralin (DP-7-AT, 1.0 mg/kg i.p.). In rats treated with GBL and a decarboxylase inhibitor, apomorphine (2.0 mg/kg i.p.) and DP-7-AT (1.0 mg/kg i.p.) induced a maximal suppression of the GBL-induced increase in the accumulation of DOPA. The effects of both apomorphine and DP-7-AT were partially inhibited by yohimbine (10 mg/kg i.p.). In inhibiting the effect of DP-7-AT, yohimbine appeared to be 100–200 times less effective than the DA antagonist haloperidol when both antagonists were administered at a fixed pretreatment time (1 h). It is concluded that yohimbine does indeed possess direct central DA autoreceptor blocking properties in vivo, and that this has to be taken into consideration if yohimbine is used as a pharmacological tool in order to achieve a selective blockade of α2-adrenoceptors.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00506241
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