Effects of dopamine on veins in humans: comparison with noradrenaline and influence of age

Objective: To compare the venoconstricting effect of dopamine with that of noradrenaline and to investigate the influence of age on the responsiveness to dopamine in human subjects. Methods: In eight young and eight elderly male subjects, increasing doses of dopamine or noradrenaline were infused into a dorsal hand vein and its diameter was measured using a linear variable differential transformer. Results: There was no significant difference between the maximum venoconstriction (E_max) for dopamine and that for noradrenaline. The infusion rate to induce 50% of E_max (ED₅₀) for dopamine in the young and elderly subjects was 363 ng · min⁻¹ and 352 ng · min⁻¹, and the ED₅₀ for noradrenaline was 40.7 ng · min⁻¹ and 43.8 ng · min⁻¹, respectively. Neither in the E_max nor in the ED₅₀ for these drugs were there significant differences between the young and elderly subjects. Conclusion: The venoconstricting effect of dopamine is 5–20 times less than that of noradrenaline, and aging does not influence the responsiveness to dopamine and noradrenaline in human subjects. Received: 29 August 1997 / Accepted in revised form: 5 February 1998     

Co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex induced by clozapine,the prototype atypical antipsychotic

Rationale. Clozapine has been shown to increase extracellular dopamine (DA) and noradrenaline (NA) in the medial prefrontal cortex (mPFC). A recent study of ours suggested that extracellular DA in the PFC originates not only from dopaminergic but also from noradrenergic terminals, its release being controlled by α₂-adrenoceptors. Objectives. Since clozapine binds to α₂-adrenoceptors, the possibility that it might co-release DA and NA was studied. Methods. By means of microdialysis coupled to HPLC with electrochemical detection, the effect of clozapine on extracellular DA and NA in the mPFC, densely innervated by DA and NA, was compared to that in the occipital cortex, equally innervated by NA but receiving few DA projections. Results. Extracellular NA was found to be the same in the two cortices, consistent with homogeneous NA innervation. On the other hand, extracellular DA in the occipital cortex was only 29% lower than in the mPFC, in spite of the scarce dopaminergic innervation in the occipital cortex. Clozapine (10 mg/kg IP) increased extracellular DA and NA not only in the mPFC (by about 320% and 290%, respectively) but also in the occipital cortex (by 560% and 230%, respectively). Administration of the α₂-agonist clonidine (0.15 mg/kg) reversed the effect of clozapine in both cortices, while the D₂-agonist quinpirole (0.1 mg/kg IP) was ineffective. Conclusions. The results suggest that clozapine, by inhibiting α₂-adrenoceptors, co-releases DA and NA from noradrenergic terminals in the occipital cortex and that the same mechanism might be responsible for the concomitant increase of the two monoamines in the mPFC. Electronic Publication     

Effects of the noradrenaline metabolites on tyrosine hydroxylase activity in guinea-pig atria

Summary The effects of noradrenaline, its five metabolites and metanephrine, were studied on tyrosine hydroxylase activity in guinea-pig atria. The deaminated metabolite, (±)-3,4-dihydroxyphenylglycol (DOPEG), was equipotent with (±)-noradrenaline in its inhibitory action on tyrosine hydroxylase activity in the homogenates of guinea-pig atria. The inhibition by DOPEG was competitive with the cofactor, reduced pteridine. The deaminated acid, 3,4-dihydroxymandelic acid (DOMA) and the O-methylated deaminated acid, 3-methoxy, 4-hydroxymandelic acid (VMA) had 1/50th and 1/30th, respectively, the potency of noradrenaline in inhibiting tyrosine hydroxylase. The rest of the metabolites did not inhibit tyrosine hydroxylase in homogenates in concentrations up to 1.0 mM. In intact guinea-pig atria noradrenaline was considerably more potent than DOPEG in inhibiting tyrosine hydroxylase. Normetanephrine 1.4×10^–4 M inhibited tyrosine hydroxylase in the intact tissue but failed to inhibited the enzyme in the homogenate even in higher concentrations. The effect of normetanephrine in the intact tissue is related to the ability of this compound to release endogenous noradrenaline.A reserpine-like agent, Ro 4-1284, did not inhibit tyrosine hydroxylase activity in the homogenate but in the intact tissue the inhibition was more than 50%. This effect of Ro 4-1284 in the intact tissue appears to be related to the releasing effects of this agent and to an increase in the axoplasmic levels of DOPEG.Since the formation of the deaminated glycol, DOPEG, represents the main metabolic pathway for the neurotransmitter in adrenergic nerve endings, the present results are compatible with the view that, in addition to the pool of extravesicular noradrenaline, the cytoplasmic concentration of DOPEG could also participate in the regulation of the activity of tyrosine hydroxylase.     

Endurance training effects on striatal D2 dopamine receptor binding and striatal dopamine metabolites in presenescent older rats

Endurance training is associated with higher binding of 3H-spiperone to striatal D2 dopamine receptors of rats sacrificed 48 h following the last exercise bout (Gilliam et al. 1984). In the present study we investigated the effects of endurance training in presenescent older rats on the relationship between steady-state levels of DA and its metabolites in striatum versus the affinity and density of striatal D2 DA receptors. Citrate synthase activity of the gastrocnemius-plantaris muscle was 29.06±2.27 mole/g wet wt in 21-month-old trained rats versus 22.88±1.13 mole/g wet wt in 21-month-old untrained animals.DOPAC levels and DOPAC/DA ratios were greater in the old controls. Endurance training was associated with lower DOPAC levels in the 21-month-old animals. Thus, endurance training may postpone selectively changes in DA metabolism over a portion of the lifespan.As expected, the number of D2 DA binding sites was reduced with age (6 months B _max:429±21 fmoles/mg protein; 21 months:355±20) with no change in affinity. The B_max of old runners was significantly higher (457 ± 38 fmoles/mg protein) than that of old controls. Thus, endurance training appears to exert a protective effect on D2 dopamine receptors during the lifespan. Taken together, the present results suggest that there may be a possible reciprocal relationship between changes in DA metabolites and DA binding as a function of exercise in presenescent older rats, and that endurance training may decelerate the effects of age both on nigrostriatal dopamine neurons and on striatal D2 dopamine receptors during a portion of the lifespan.     

HPLC-ECD法测定大鼠脑微透析液中的多巴胺及其代谢产物

目的:建立应用常规高效液相-电化学法(HPLC-ECD)测定大鼠脑微透析液中多巴胺(DA)及其代谢产物3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)的方法。方法:将探针插入大鼠右侧纹状体,在清醒自由活动状态下,用Ringer氏液以1.5μl.min-1的速度灌流,每20 min收集1管透析液,将其注入HPLC-ECD,考察本方法的专属性、线性范围、精密度和准确度等,并对其中所含的DA、DOPAC、HVA进行测定。结果:3种物质在12.5~250μg.L-1范围内线性关系良好,高、中、低3种浓度的回收率分别为98.33%、102.67%、92.33%,各物质的日内RSD值分别为3.3%、3.4%、2.5%;日间RSD值为4.2%、2.3%、5.6%。大鼠脑微透析液中的DOPAC及DA、HVA的含量分别为1.79±0.07、0.45±0.02、1.67±0.05μg.ml-1(n=6)。结论:本方法简便、准确、稳定,可用于应用脑微透析技术进行的DA相关疾病的基础研究。     

Release of vesicular noradrenaline in the rat tail artery induced by cocaine

Summary The effects of cocaine on overflows of endogenous noradrenaline and DOPEG from isolated rat tail arteries were examined. 1. Both overflows increased progressively with increasing concentration of cocaine, while the (NA overflow)/(DOPEG overflow) ratio first increased and then decreased. The changes in the overflows induced by cocaine (0.1 mmol/l) appeared reversible. 2. Exposure of the tissue for 30 min to cocaine, 1 mmol/l, resulted in a significant decrease in the proportion of storage vesicles containing electron-dense cores. 3. The changes in overflows of noradrenaline and DOPEG induced by cocaine (0.1 mmol/l) were unaffected by the presence of desipramine (0.1 mol/l) or removal of extracellular Ca²⁺. The effect of cocaine on the overflow of noradrenaline was potentiated by prior inhibition of MAO with clorgyline. 4. Exposure of segments to a Ca²⁺-free, high K, low Na incubation medium was accompanied by increased overflow of noradrenaline. Cocaine (0.1 mmol/l) reduced the overflow of noradrenaline to about a half, and substantially increased the overflow of DOPEG. 5. The increase in the overflow of DOPEG from segments bathed in HEPES-buffered solutions, the pH of which ranged from 6.80 to 7.38, was approximately proportional to the calculated concentration of unprotonated (uncharged) cocaine. 6. Quantitatively similar changes in the overflows were observed when norcocaine was substituted for cocaine. Ecgonine methyl ester was much less potent than cocaine, and O-benzoyl ecgonine was ineffective. 7. The small increases in the overflow of noradrenaline observed at relatively low concentration (<30 mol/l) of cocaine can be attributed primarily to inhibition of reuptake of the released transmitter by the cocaine- and desipramine-sensitive amine carrier. The overflows of NA and DOPEG in the presence of higher concentrations of the alkaloid exhibit features compatible with the following hypothesis: (A) Cocaine is translocated across the axonal membrane mainly in the form of the unprotonated species, a large fraction of which is reprotonated upon the entry into the axon. (B) Cocaine releases noradrenaline from storage vesicles into the extravesicular space, where the bulk of the amine is converted to DOPEG. (C) Efflux of the remaining noradrenaline from the axon is not mediated by the Na⁺-dependent, cocaine- and desipramine-sensitive neuronal amine carrier. It seems to represent uncoupled efflux of the protonated form of noradrenaline.Abbreviations DOPEG 3,4-dihydroxyphenylethylene glycol - DOMA 3,4-dihydroxymandelic acid - HEPES N-(2-hydroxyethyl)piperazine-N-ethanesulfonic acid - MAO monoamine oxidase - MOPEG 3-methoxy-4-hydroxyphenylethylene glycol - NA (–)noradrenaline - pH_j pH in the extravesicular space of the axon - pH_o pH of the bathing solution - pK_a negative logarithm of the dissociation constant This study was supported by the British Columbia Heart Foundation Send of fprint requests to V. Palaty at the above address     

Alterations in cerebrospinal fluid dopamine metabolites following physostigmine infusion

The effect of IV physostigmine administration on the cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) in normal subjects was determined. After an adjustment for differing CSF concentrations of probenecid, physostigmine was found to elevate CSF HVA and DOPAC concentrations. The authors discuss these changes in CSF HVA and DOPAC and their possible relationship to the ability of physostigmine to decrease the symptoms of some patients with tardive dyskinesia.     

Effect of chronic clonidine treatment on the turnover of noradrenaline and dopamine in various regions of the rat brain

Summary The turnover of noradrenaline (NA) and dopamine (DA) was estimated in various rat brain regions by measuring the depletion of the amines after inhibition of their biosynthesis by -methyltyrosine. Acute treatment with clonidine (0.1 mg/kg) reduced NA turnover in the brain stem, hypothalamus and rest of the brain but had no effect on DA turnover in the corpus striatum and rest of the brain. After chronic clonidine treatment (0.1 mg/kg, twice daily for 15 days), NA turnover was not affected by an additional injection of clonidine in the brain stem or in the hypothalamus but was still markedly reduced in the rest of the brain. In addition, DA turnover was reduced in the corpus striatum and rest of the brain, an effect which was also observed after a single injection of a high dose of clonidine (1 mg/kg). These findings suggest that a chronic administration of clonidine may cause regionally differential changes in the sensitivity of central NA receptors.     

Assessment of cerebrospinal fluid levels of dopamine metabolites by gas chromatography

The acid metabolites of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined in lumbar cerebrospinal fluid (CSF) by a new procedure. After gas Chromatographic separation, the pentafluoropropionyl 2,2,3,3,3-pentafluoro-1-propionyl esters of DOPAC and HVA were analyzed by electron capture detection. Normal HVA levels were quantitated in as little as 0.1 ml CSF. No significant amounts of DOPAC (< 1 ng/ml) were found in any of the drug-free samples analyzed. Levels of DOPAC increased only marginally in the CSF of patients receiving acute or chronic doses of lDopa. Baseline HVA levels ranged from 4.5–50 ng/ml with a mean value of 23 ng/ml. These studies demonstrate that HVA is the major dopamine metabolite in human CSF.Supported by a grant from the NIMH No. MH 21638-03 and a Research career development award No. 1 K04 GM 40793-05 to S. W.     

Inhibition of the turnover of the brain dopamine after treatment with the gammaaminobutyrate: 2-oxyglutarate transaminase inhibitor aminooxyacetic acid

Summary Treatment with aminooxyacetic acid (AOAA, 50 mg/kg i.p.) did not significantly change the concentrations of dopamine and noradrenaline in the rat brain. It markedly and similarly decelerated the disappearance of dopamine in the corpus striatum and the limbic system after treatment with dl--methytyrosine methylester (-MT, 250 mg/kg i.p., 4 h) and accelerated the disappearance of noradrenaline. It also blocked the acceleration of the -MT-induced dopamine, but not noradrenaline, disappearance caused by haloperidol. Administration of gamma-hydroxybutyric acid (GHBA, 1.5+1.0 g/kg i.p.) resulted in a larger retardation of the -MT-induced dopamine disappearance which was about the same in the corpus striatum and the limbic system. Treatment with GHBA also increased the endogenous dopamine and this effect was significantly larger in the corpus striatum than in the limbic system like after an axotomy. The effect of AOAA may be due to accumulation of GABA inhibiting the cell bodies of the dopaminergic neurones.     

The K+-induced increases in noradrenaline and dopamine release are accompanied by reductions in the release of their intraneuronal metabolites from the rat anterior hypothalamus

Summary The novel technique of microdialysis has been used to examine the basal and K⁺-induced release of catecholamines and metabolites from the anterior hypothalamus of the urethane-anaesthetized rat in vivo. A high pressure liquid chromatographic assay was developed to simultaneously measure endogenous noradrenaline, dopamine and their intraneuronal metabolites 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxyphenylacetic acid (DOPAC) respectively, in each 60 l dialysate sample. The effect of replacing Ca²⁺ in the perfusion fluid with a low concentration of Cd²⁺, which blocks Ca²⁺ effects, was also studied. Increasing the K⁺ concentration in the perfusion fluid elicited a concentration-dependent increase in noradrenaline and dopamine release. In contrast, there were marked reductions in DOPEG and DOPAC which were not concentration-dependent. In the Ca²⁺-depleted conditions, the K⁺-induced increase in amine release was significantly attenuated, but the reductions in the metabolites were not affected. We suggest that the mechanisms contributing to the observed reductions in the metabolites may be inhibition of neuronal reuptake, an increase in neuronal efflux, an enhancement of vesicular uptake and a decrease in vesicular efflux. Send offprint requests to E. Badoer at the above address     

Changes in drug-induced stereotyped behavior after 6-OHDA lesions in noradrenaline neurons

Drug-induced stereotyped behaviors are often assessed by rating scales where the eventual appearance of sniffing, licking, and biting are rated as increasing intensity of dopaminergic stimulation. A 6-OHDA induced bilateral lesion (4×3-8 g/4 l 6-OHDA) in the ascending noradrenaline neurons, lateral to the medial raphe nucleus, of 180 g Wistar rats, affecting selectively noradrenaline and not dopamine or 5-hydroxytryptamine neurons, caused a change in the d-amphetamine sulphate (5–3 mg/kg s.c.) and phenethylamine hydrochloride (40 mg/kg) induced stereotyped sniffing behavior to the performance of discontinuous or continuous licking behavior; biting/gnawing was rarely induced. The site of the lesion and the partial antagonism of 6-OHDA by the uptake inhibitor protriptyline indicate a noradrenergic influence on the behavioral expression of the dopaminergically mediated stereotyped behavior.     

The roles of noradrenaline and dopamine in contraversive circling behaviour seen after unilateral electrolytic lesions of the locus coeruleus

Unilateral electrolytic lesions of the locus coeruleus in rats result in spontaneous ipsiversive rotation, which is then replaced by contraversive rotation. One week after lesioning, when spontaneous turning ceases, apomorphine and d-amphetamine elicit contraversive circling behaviour, which was not affected by noradrenergic receptor blockade but was abolished by dopamine receptor blockade. The drug-induced contraversive circling response was also reproduced by piribedil but not clonidine. Combined unilateral electrolytic locus coeruleus and substantia nigra lesions on the same side resulted in apomorphine- and d-amphetamine-induced ipsilateral rotational behaviour which was indistinguishable from that seen with substantia nigra lesions alone. In rats with unilateral locus coeruleus lesions, the dose of intrastriatally injected apomorphine required to produce circling was less on the lesioned than the non-lesioned side. Direct injection of noradrenaline into one substantia nigra caused contraversive circling. Direct injection of phenoxybenzamine into one substantia nigra followed by apomorphine caused ipsiversive circling.The results suggest that the circling behaviour seen after unilateral locus coeruleus lesions depends on an asymmetry of striatal dopamine receptor activity and are consistent with a proposed coeruleus—nigral noradrenergic pathway, which enhances impulse flow in the dopaminergic nigrostriatal system.     

Decrease in dopamine,its metabolites and noradrenaline in cerebrospinal fluid of schizophrenic patients after withdrawal of long-term neuroleptic treatment

Dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), noradrenaline (NA), and 5-hydroxyindolacetic acid (5HIAA) were measured in cerebrospinal fluid (CSF) of 15 chronic schizophrenic patients before and 2 weeks after withdrawal of long-term neuroleptic treatment. Total neuroleptic-like activity in serum (NLA) was determined at the same times. Levels of DA and its metabolites (DOPAC and HVA) and NA were significantly reduced after the discontinuation of neuroleptic treatment. No change was observed in 5HIAA values. NLA was substantially reduced, but still remained detectable. The decrease in DA, DOPAC, and HVA all showed positive correlations with each other, and correlated negatively with NLA measured after 2 weeks. Our data implies that the decrease in DA turnover is the result of the discontinuance of DA receptor blockade, while the change in NA level is independent of it.This work was supported by the State Office for Technical Development, Hungary     

Cathinone affects dopamine and 5-hydroxytryptamine neurons in vivo as measured by changes in metabolites and synthesis in four forebrain regions in the rat

Cathinone is an active ingredient in the leaves of the Khat shrub. Cathinone affects behavior, neurochemistry and electrophysiology in a manner similar to the stimulants amphetamine, cocaine and methylphenidate. The present study extended these studies by evaluating the effects of (+/-)cathinone on dopamine (DA) and 5-hydroxytryptamine (5-HT)-containing neurons in several regions of the rat brain in vivo. An index of the rate of synthesis of DA and 5-HT in vivo was determined in the nuclei caudatus putamen (CP), accumbens (NA), amygdaloideus centralis (AC), septi lateralis (SL), preopticus pars suprachiasmatica (PSCN) and dorsomedialis (hypothalami; DMN) of male rats (175-225 g) by measuring the concentration of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) after the administration of NSD 1015 (100 mg/kg, i.p.) an inhibitor of aromatic L-amino acid decarboxylase. Concentrations of DA, 5-HT and their major metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), respectively, were analyzed by high pressure liquid chromatography coupled to an electrochemical detector. Cathinone decreased levels of DOPAC in a time- and dose-related manner in the caudatus putamen, accumbens, amygdaloideus centralis and septi lateralis with the peak effect occurring 30-60 min after a dose of 6 mg/kg (i.p.). Cathinone had no effect on DOPAC in the preopticus pars suprachiasmatica or dorsomedialis (hypothalami). The drug also decreased the accumulation of DOPA in the caudatus putamen, accumbens, amygdaloideus centralis and septi lateralis, but in the preopticus pars suprachiasmatica and dorsomedialis (hypothalami), there was no effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline,dopamine and 5-hydroxytryptamine

The interaction of sympathomimetic amines with the transport of ³H-noradrenaline (³H-NE), ³H-dopamine (³H-DA) and ³H-5-hydroxytriptamine (³H-5-HT) were investigated in rat hypothalamic (³H-NE) and striatal (³H-DA and ³H-5-HT) synaptosomes. Modifications in the phenylethylamine structure led to changes in activity towards biogenic amine uptake and release: (a) the introduction of a β-OH group led to compounds less active in inhibiting uptake and stimulating release of ³H-NE, ³H-DA and ³H-5-HT, with the exception of ³H-NE release which was stimulated more by unlabeled 1-NE than by DA; (b) the introduction of phenolic -OH groups always led to compounds which were stronger uptake inhibitors and releasers of the three biogenic amines; (c) the α-methylation increased the potency towards uptake inhibition and release stimulation, with the exception of ³H-NE release: in fact, the releasing activity of phenylethylamine was suppressed by α-methylation; (d) the introduction of a -Cl group in the para position selectively potentiated the effects on ³H-5-HT uptake and release and generally depressed those on catecholamine transport.     

Effects of drugs influencing monoamine mechanisms on the increase in brain dopamine produced by axotomy or treatment with gammahydroxybutyric acid

Summary The influence of blockade or stimulation of dopamine (DA) receptors on the selective increase in brain DA seen after axotomy or injection of gammahydroxybutyric acid (sodium form, 1.5 g/kg i.p.) was studied in rats. The increases were not changed after blockade of the DA receptors by haloperidol but were slightly reduced after stimulation of these receptors by apomorphine. Since pretreatment with haloperidol counteracted this effect of apomorphine, a diminished stimulation of DA receptors may partially be responsible for the increase in brain DA seen when the nerve impulse flow has been blocked in the DA neurones by axotomy or treatment with gammahydroxybutyric acid. The NA content was usually somewhat lowered on the lesioned side and this reduction was not changed after treatment with haloperidol, apomorphine or amphetamine.The increase in brain DA usually observed after axotomy was not found when the rats were also treated with reserpine and nialamide. This effect indicates that the negative feed-back of cytoplasmic DA on the DA synthesis operates also in the absence of nerve impulses.Injection of amphetamine before or after axotomy or treatment with gammahydroxybytyric acid markedly inhibited the increase in brain DA, probably due to release of newly synthesized DA.Data presented in part at the Animal Pharm, Uppsala, June 13, 1972 (Andén and Magnusson, 1972).     

Functional antagonism between dopamine and noradrenaline within the caudate nucleus of cats: A phenomenon of rhythmically changing susceptibility

Two aspects of the functional interaction between the neurotransmitters dopamine (DA) and noradrenaline (NE) were studied: the role of NE within brain structures marked by DA terminals and the occurrence of annual changes in their functional interaction. The behavioral changes produced by single or combined administration of DA, (3,4-dihydroxyphenylamino)-2-imidazoline (DPI), ergometrine, ET-495, NE, oxymetazoline, and phentolamine into the caudate nucleus of freely moving cats were analyzed. NE and oxymetazoline produced effects that differed from those elicited by DA or DPI. NE-dependent effects were antagonized by phentolamine, and DA- or DPI-induced effects were antagonized by ergometrine. Ergometrine, NE, and oxymetazoline were effective in November, December, and January, lost their effectiveness in March, April, and May, regained it in July, and lost it again in August, September, and October. The annual pattern of DA, DPI, and phentolamine on the other hand, was just the opposite. DA agonists suppressed NE- or oxymetazoline-induced effects, while the DA antagonist suppressed phentolamine-induced effects. Noradrenergic agents were unable to modulate the DA-dependent effects under certain circumstances. It is concluded that (1) NE-dependent processes within the feline caudate nucleus inhibit DA-dependent processes within this structure, and (2) there exists a reciprocal relationship between the annual changes in the feline's susceptibility to DA, DPI, and phentolamine, on the one hand, and to ergometrine, NE, and oxymetazoline, on the other hand.     

Role of brain noradrenaline in morphine-induced stereotyped behaviour

The injections of morphine into rats which had been made tolerant to morphine produced stereotyped sniffing, licking and biting reminiscent of amphetamine-stereotypy. Pretreatment with drugs acting on the brain catecholamines such as reserpine, H 44/68, FLA-63 and receptor blockers could inhibit this behaviour. Comparison between morphine and amphetamine stereotypy indicated that brain noradrenaline plays a more important role than dopamine in morphine induced stereotyped behaviour, in contrast to amphetamine stereotypy where dopamine is the most important brain amine. The result of experiments with intraventricular injections of noradrenaline supported this conclusion, because the noradrenaline suppressed the blocking action of FLA-63 on morphine-induced stereotypy.