A TRH analog (DN-1417). Effects on the levels of monoamines and the metabolites in the various brain regions in rats

The effects of a TRH (thyrotropin-releasing hormone) analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate), on the levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and the metabolites in the various brain regions of rats were determined by means of high performance liquid chromatography with electrochemical detection. DN-1417 (20 mg/kg, i.p.) produced marked decreases in the levels of NE, DA and 5-HT, especially in the nucleus accumbens, striatum and hypothalamus. The maximum effect was observed at 15 min after the administration. DA metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased significantly in the nucleus accumbens, striatum and hypothalamus, whereas 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid remained unchanged. 3-Methoxytyramine increased significantly in the nucleus accumbens and striatum. Two week chronic administration of DN-1417 (20 mg/kg, i.p.) increased the levels of DA and NE in the nucleus accumbens and DA in the striatum. These results suggest that DN-1417 stimulates the turnover of the cerebral monoamines, especially the release of DA from the nucleus accumbens and striatum in the mesolimbic and nigro-striatal DAergic systems.     

Tianeptine increases the extracellular concentrations of dopamine in the nucleus accumbens by a serotonin-independent mechanism.

The effect of various doses of tianeptine on the extracellular concentrations of dopamine was studied in the striatum and nucleus accumbens of the rat. At 5 (but not 2.5) mg/kg intraperitoneally, tianeptine increased the extracellular dopamine only in the nucleus accumbens. At 10 mg/kg, the effect was also seen in the striatum but it was less marked and shorter-lasting. At 10 mg/kg (i.p.), tianeptine significantly raised the extracellular concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in both regions. The effect of 10 mg/kg tianeptine on dopamine and its metabolites was not significantly changed in animals which had received this dose twice daily for 15 days. Intracerebroventricular administration of 150 micrograms/20 microliters 5,7-dihydroxytryptamine, which markedly depleted serotonin in the brain, did not modify the effect of 10 mg/kg tianeptine on the extracellular concentrations of dopamine and HVA in the nucleus accumbens but reduced the effect on DOPAC. Various doses of tianeptine (1, 3 and 10 mg/kg i.p.) did not change the synthesis of serotonin and dopamine in the striatum and nucleus accumbens. The results show that tianeptine increased the extracellular concentrations of dopamine more in the nucleus accumbens than in striatum. The effect on the output of DA in the nucleus accumbens could be involved in the antidepressant activity of tianeptine.     

Effects of trimethyltin on dopaminergic and serotonergic function in the central nervous system

The effects of trimethyltin (TMT) administration on regional concentrations of dopamine (DA), serotonin (5-HT), and their metabolites were determined. Acute administration of 3 or 7 mg/kg TMT (as the chloride) to adult male Long-Evans rats caused alterations in both dopaminergic and serotonergic function in brain at 7 days posttreatment. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations were decreased in the nucleus accumbens of rats treated with 7 mg/kg, with a trend occurring with the 3-mg/kg dose group. Conversely, concentrations of DA or DOPAC were not altered in striatum, olfactory tubercle, septum, or amygdala/pyriform cortex. Administration of 3 mg/kg TMT decreased the concentration of serotonin in striatum and nucleus accumbens, and increased the concentration of 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus. The 7-mg/kg dose resulted in increased concentrations of 5-HIAA in striatum, nucleus accumbens, septum, amygdala/pyriform cortex, and hippocampus, and also decreased the concentration of 5-HT only in amygdala/pyriform cortex. The ratio of 5-HIAA to 5-HT (an indirect estimate of serotonin turnover) was increased in all brain regions of rats treated with 7 mg/kg, and in nucleus accumbens and amygdala/pyriform cortex of rats treated with 3 mg/kg. Conversely, no alteration in the DOPAC to DA ratio was found in any region of brain in rats killed at 7 days, nor was there a change in dopamine receptors (as measured by [³H]spiperone binding) in rats treated with 7 mg/kg TMT and killed 7 days following exposure. Thus, the acute sequelae of TMT neurotoxicity appears to involve primarily serotonergic systems, and these effects may be related to the behavioral effects resulting from TMT administration.     

Effect of acute and chronic treatment of rats with the putative anxiolytic drug ipsapirone on the turnover of monoamine transmitters in various brain regions. A comparison with the 5-HT1A agonist 8-OH-DPAT.

A fourteen-days treatment (twice a day) of male Wistar rats with the putative anxiolytic ipsapirone (10 mg/kg po) and the selective 5-HT1A agonist 8-OH-DPAT (1 mg/kg ip) induced changes in the turnover of serotonin and catecholamines in various regions of the brain. In contrast to 8-OH-DPAT, ipsapirone stimulated the development of tolerance in serotonin neurons in the hypothalamus, hippocampus, cortex and striatum. Nevertheless, adaptative changes were not produced by ipsapirone in dopamine neurons in the striatum or nucleus accumbens, or in noradrenaline neurons in the hypothalamus, hippocampus or cortex. The centrally active metabolite of ipsapirone 1-PP, which has adrenolytic properties, seems to be responsible for the effects on the dopamine and noradrenaline turnover.     

MIF-1: effects on norepinephrine, dopamine and serotonin metabolism in certain discrete brain regions

A single injection of melanocyte-stimulating hormone inhibitory factor (MIF-1) in a dose of 3 mg/kg IP produced no significant effect on dopamine turnover. However, a dose of 5 mg/kg increased striatal tyrosine hydroxylase activity by 25% and homovanillic acid level by 27% when compared to control values. No change in either parameter was detected in olfactory tubercles. Dopamine levels also were elevated in striatum, pons-medulla and cerebral cortex in rats receiving 5 mg/kg dose of MIF-1. In olfactory tubercles, dopamine levels were however, reduced to 71% of control values taken as 100%. The concentration of norepinephrine tended to increase in several brain areas examined but, the change was statistically significant only in olfactory tubercles and cerebral cortex. The level of norepinephrine metabolite, 3-methoxy-4-hydroxyphenylethylene glycol, was lowered to 63% in whole brain of animals given MIF-1 at the dose of 5 mg/kg. These data suggest that MIF-1 enhances the turnover of dopamine and norepinephrine in the brain. However, MIF-1 treatment seemed to produce no consistent change in brain serotonin turnover. In striatum and cortex, this neuropeptide increased serotonin but elevated the level of its metabolite, 5-hydroxyindoleacetic acid indicating that the release of this brain amine was decreased in these two brain regions. The levels of 5-hydroxyindoleacetic acid were enhanced in hypothalamus and pons-medulla regardless of the dose of MIF-1 administered.     

Release of dopamine is reduced by diazepam more in the nucleus accumbens than in the caudate nucleus of conscious rats

The effects of 1-20 mg/kg diazepam were studied on the extracellular concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens and striatum of conscious rats, using intracerebral microdialysis. Five, but not 1 mg/kg diazepam significantly reduced extracellular DA, DOPAC and HVA in the nucleus accumbens. Twenty mg/kg diazepam significantly reduced extracellular DA, DOPAC and HVA in the striatum. A significant effect on striatal DOPAC, but not on DA and HVA, was seen with 10 mg/kg diazepam, while no changes were found with 5 mg/kg diazepam. The results suggest that diazepam reduces the release and metabolism of DA in the nucleus accumbens more than in the striatum.     

JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity, increases extracellular dopamine in the prefrontal cortex, but not in the striatum and the nucleus accumbens of rats

In behavioral and receptor binding studies, 5-(4-methylpiperazin-1-yl)-8-chloro-pyridol[2,3b] [1,5]benzoxazepine (JL13) shows an atypical antipsychotic profile. We used microdialysis in awake rats to study the effects of various intraperitoneal doses of JL13 on extracellular concentrations of dopamine in the prefrontal cortex, nucleus accumbens and striatum. JL13 at 20 mg/kg and 40 mg/kg dose-dependently raised extracellular dopamine (234% and 434% of basal levels at peak, respectively) in the prefrontal cortex whereas lower doses (5 mg/kg and 10 mg/kg) had no effect. Extracellular concentrations of dihydroxyphenylacetic acid and homovanillic acid were also significantly increased in the prefrontal cortex of rats given 40 mg/kg JL13 (310% and 230% of basal levels, respectively). At 20 mg/kg and 40 mg/kg JL13 did not affect the extracellular concentrations of dopamine and its metabolites in the striatum and nucleus accumbens. The mechanisms by which JL13 increases cortical dopamine release and the significance for potential antipsychotic efficacy are discussed.     

Reduced metabolism and turnover rates of rat brain dopamine, norepinephrine and serotonin by chronic desipramine and zimelidine treatments

As part of of an ongoing effort to compare changes in whole body turnover of catecholamines and serotonin in man with those induced by antidepressants in the rat brain, we have evaluated the chronic effects of desipramine (DMI) and zimelidine (ZMI) on brain catecholamines and serotonin in the rat. The amines and metabolites measured include norepinephrine (NE), dopamine (DA) and their metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Three brain areas were analysed; the hypothalamus, caudate nucleus and frontal cortex. Chronic DMI and ZMI reduced hypothalamic MHPG and caudate nucleus DA metabolites, in particular HVA. Both drugs reduced NE and DA turnover rates (estimated after alpha-methyl-p-tyrosine injection) and the rate of MHPG formation in the hypothalamus (estimated after pargyline treatment). They did not change NE turnover rate, but reduced DA turnover rate and rate of HVA formation in the caudate nucleus. Chronic DMI but not ZMI reduced DOPAC rate of formation in the caudate nucleus. Apparently changes in DA turnover and metabolism produced by these antidepressants are better related to changes in HVA than DOPAC concentrations. Similar to their influence on hypothalamic and caudate nucleus catecholamines, both chronic DMI and ZMI produced changes in serotonin concentration in the caudate nucleus and frontal cortex serotonin that suggest a reduction in its turnover rate and metabolism. The reduction in NE turnover in hypothalamus is consistent with the effects of chronic DMI and ZMI on whole body NE turnover observed in man.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of MK-771, a novel TRH analog,on brain dopaminergic and serotonergic systems

The effect of acute treatment with MK-771, a thyrotropin-releasing hormone analog, has been investigated on the synthesis and release of dopamine and 5-hydroxytryptamine in rat brain. Single injection of MK-771 in doses of 10 and 15 mg/kg produced a rise in tyrosine hydroxylase activity as well as homovanillic acid level in striatum (a site of nigrostriatal dopamine system) and olfactory tubercles (a site of mesolimbic dopamine system). The dopamine levels remained unchanged (olfactory tubercles, hippocampus) or decreased (striatum, hypothalamus, pons-medulla) after MK-771 treatment. Acute MK-771 injection at the dose of 15 mg/kg increased mid-brain tryptophan hydroxylase activity and tryptophan levels by 26% and 55%, respectively. A consistent increase in the levels of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid was reported in several brain areas. These data suggest that MK-771 elicits a marked increase in the synthesis and turnover of brain dopamine and 5-hydroxytryptamine.     

DISSOCIATION OF INCREASED 5-HYDROXYINDOLEACETIC ACID LEVELS AND PHYSICAL DEPENDENCE: THE EFFECTS OF NALOXONE

1. A slow release emulsion of naloxone (naloxone SR) was administered subcutaneously to rats in an attempt to induce physical dependence of the morphine type. 2. Naltrexone (2.5 mg/kg), injected i.p., failed to elicit an abstinence syndrome in rats treated with 75, 100 or 150 mg/kg naloxone SR for 24, 48, or 72 h. 3. Naloxone SR had no effect on the whole brain levels of noradrenaline, dopamine, homovanillic acid or serotonin. 4. Naloxone SR caused an apparent dose-related increase in the brain levels of 5-hydroxyindoleacetic acid. 5. These results show that while naloxone does not induce physical dependence of the morphine type, it may, like morphine, increase the brain serotonin turnover rate. 6. It is proposed that the increase in brain serotonin turnover rate may not be causally related to physical dependence on morphine-like drugs but may be a property of drugs containing the basic opiate molecular structure.     

Effects of mCPP on the extracellular concentrations of serotonin and dopamine in rat brain.

Intravenous administration of m-chloro-phenylpiperazine (mCPP) (0.25 or 2.5 mg/kg) induced a marked and dose-related increase in extracellular concentrations of serotonin in hippocampus (300-1,400% of baseline) as measured using in vivo microdialysis in awake male Wistar rats of the spontaneously hypertensive (SH) strain. Indicating that the effect of mCPP was caused by a reversal of the serotonin transporter, it was antagonized by pretreatment with the serotonin re-uptake inhibitor citalopram (10 mg/kg) but was unaffected by local administration of the sodium channel blocker tetrodotoxin (TTX; 1 microns). mCPP was also shown to induce an increase in extracellular concentrations of dopamine in the nucleus accumbens and the striatum of SH rats and in the nucleus accumbens of rats of the Sprague-Dawley (SD) strain; this effect of mCPP was, however, much weaker (125-170% of baseline) than the effect on serotonin; moreover, it seems to be TTX-sensitive. In anesthetized SD rats, mCPP induced a moderate reduction of nigral dopamine cell firing rate; supporting the assumption that this effect is secondary to the observed increase in dopamine release, it was blocked by pretreatment either with the dopamine synthesis inhibitor alpha-methyl-para-tyrosine or with the dopamine D2 receptor antagonist haloperidol. In conclusion, the results suggest that mCPP induces a marked, TTX-insensitive increase in serotonin release in rat brain, but only a modest and TTX-sensitive increase in the extracellular levels of dopamine.     

The CB(1) cannabinoid receptor antagonist AM251 attenuates amphetamine-induced behavioural sensitization while causing monoamine changes in nucleus accumbens and hippocampus

Endogenous cannabinoids modulate the activity of dopamine reward pathways and may play a role in the development of behavioural sensitization to psychostimulants. Here, we investigated the effects of the CB(1) cannabinoid receptor antagonist AM251 on amphetamine-induced locomotor sensitization in mice. Furthermore, we measured post-mortem monoamine concentrations in nucleus accumbens and hippocampus after termination of the behavioural tests. The results can be summarized as follows: Mice pre-treated with AM251 (3 mg/kg; i.p.) showed less sensitivity to the psychomotor stimulant as well as locomotor sensitizing effects of amphetamine (2 mg/kg; i.p.) resembling previous results obtained with CB(1) receptor-deficient animals. Furthermore, the behavioural effects of AM251 were paralleled by increased dopamine concentration in nucleus accumbens and increased serotonin concentration/turnover rate in hippocampus, respectively. The present data indicate that under normal conditions activation of the CB(1) receptor facilitates those adaptive responses elicited by repeated psychostimulant administration and resulting in sensitization, possibly by reducing dopamine biosynthesis and serotonin turnover in the nucleus accumbens and hippocampus.     

Effect of low-dose sulpiride on dopamine metabolism in rat nucleus accumbens and locomotor activity: studies with intracerebral dialysis]

Changes in the concentration of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA), were determined sequentially in freely moving rats by using a brain dialysis method. The purpose of this study was to investigate the relationship between changes in the dopamine metabolism in the nucleus accumbens and locomotor activities following low-dose (5 mg/kg) sulpiride administration. The DA content in the dialysis fluid rose significantly 4 to 6 h after sulpiride administration. The DOPAC content rose significantly 6 h after sulpiride administration. The HVA content did not show a significant change. A slight increase of locomotor activity was found, but it was not statistically significant. The elevation of DA release in nucleus accumbens by sulpiride might relate to the clinical efficacy of low-dose administration of this drug for mood disorders.     

Brain 3-methyoxytyramine varies inversely with blood glucose in decapitated rats

Concentrations of the dopamine metabolite, 3-methyoxytyramine, were decreased significantly in the corpus striatum and nucleus accumbens of rats 30 min after the IP injection of D-glucose (2 g/kg). Conversely, 90 min after the administration of regular insulin (6 U/kg), significant increases in the concentrations of 3-methoxytyramine were observed in these two brain regions. Brain levels of the major metabolites of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, did not correlate well with blood glucose concentration. The significant negative correlation of blood glucose with striatal and accumbens 3-methoxytyramine suggests an inverse relationship between dopamine metabolism and blood glucose concentration, that may be secondary to decapitation-induced anoxia.     

5-HT3 Receptor Antagonist MDL 72222 Dose-Dependently Attenuates Cocaine- and Amphetamine-Induced Elevations of Extracellular Dopamine in the Nucleus Accumbens and the Dorsal Striatum

Abstract: The effects of a 5-HT₃ receptor antagonist MDL 72222 on cocaine- and amphetamine-induced increases in extracellular dopamine in the nucleus accumbens and the dorsal striatum were studied with microdialysis technique using halothane anaesthesized rats. Dopamine and its metabolites were measured by HPLC with electrochemical detection. Cocaine elevated extracellular dopamine in the nucleus accumbens and to a lesser extent in the dorsal striatum, but it did not affect dopamine metabolites, 3 ,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid. Pretreatment with MDL 72222 (25-100 μg/kg) dose-dependently attenuated cocaine-induced elevation of dopamine in both of the nuclei studied. Amphetamine elevated extracellular dopamine and reduced DOPAC and homovanillic acid equally in the nucleus accumbens and in the dorsal striatum. MDL 72222 also attenuated the amphetamine-induced elevation of extracellular dopamine concentration in both brain areas studied, but first at a dose of 100 μg/kg. The different potencies of the interactions of the 5-HT₃ receptor antagonist with cocaine and amphetamine could be related to the different mechanisms by which these drugs primarily elevate extracellular dopamine.     

Hypophysectomy does not prevent increased cerebral dopamine turnover following sulpiride administration

Hypophysectomy is claimed to prevent increased forebrain dopamine turnover produced by administration of sulpiride. We have measured the increase in dopamine metabolite concentrations caused by sulpiride following surgical removal of the pituitary. In saline-treated control animals and in hypophysectomized rats 1 week or 1 month following surgery, administration of sulpiride caused marked elevations of striatal, nucleus accumbens and tuberculum olfactorium, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations which were maximal 4-8 h following drug administration. The maximal increases in nucleus accumbens and tuberculum olfactorium were generally comparable in control and hypophysectomized animals, except for a greater increase in HVA levels in the nucleus accumbens 1 month following hypophysectomy. However, maximal increases in HVA and DOPAC in striatum were more pronounced in hypophysectomized rats 1 week or 1 month following surgery compared with control animals. At 30 min following sulpiride administration only inconsistent changes in dopamine turnover were observed in both control and hypophysectomized rats. Hypophysectomy does not prevent sulpiride from increasing forebrain dopamine turnover suggesting this is due to a direct interaction with cerebral dopamine receptors.     

Association between depressive behavior and absence of serotonin–dopamine interaction in the nucleus accumbens

RATIONALE: Current hypotheses on the etiology of depression attribute the disorder to alterations in serotonin and norepinephrine neurotransmission. However, the relationship between these alterations and depressive behavior is poorly understood. Conversely, an interaction between the serotonergic and dopaminergic systems in the nucleus accumbens has been established. Since motivation and hedonia have been associated with dopamine release in the nucleus accumbens, we decided to test its modulation by serotonin in relation to depressive-like behavior. OBJECTIVES AND METHODS: The extracellular dopamine levels in the nucleus accumbens were studied in vivo in Flinders Sensitive Line (FSL, a rat model of depressive behavior) and control rats, before and after antidepressant treatment. Rats were chronically treated with the antidepressants desipramine (5 mg/kg/day) and paroxetine (7.5 mg/kg/day) for 18 consecutive days. As a measure of depressive behavior we used a modified swim test. The release of dopamine in response to local serotonin application was monitored using the microdialysis technique. RESULTS: Serotonin (0.5 microM) facilitated dopamine release in the nucleus accumbens of control rats. In FSL rats, basal extracellular dopamine levels in the nucleus accumbens were 40% lower than in control rats and did not increase in response to serotonin stimulation. However, chronic antidepressant treatment of the FSL rats normalized the serotonin-dopamine interaction as well as their behavioral deficiencies. CONCLUSIONS: The inability of serotonin to stimulate dopamine release in the nucleus accumbens, thereby leading to anhedonia and lack of motivation, may therefore be an essential factor in the onset of depression and a target for modulation by antidepressant drugs.     

Effects of trepelennamine on brain monoamine turnover in morphine dependent and abstinent mice

Previous studies have reported that the histamine H₁ receptor blocker tripelennamine potentiates morphine withdrawal. In this paper, the in vivo effects produced by tripelennamine on the turnover of serotonin (5-HT), dopamine (DA) and noradrenaline (NA) in the whole brain, excluding the cerebellum, were studied in control, morphine-dependent (by SC implantation of a 75 mg morphine pellet) and morphine-dependent male CD1 mice just before naloxone-precipitated withdrawal. Tripelennamine (1–10 mg/kg) was administered SC 45 min before the animals were killed. Serotonin, 5-hydroxyindole-3-acetic acid (5-HIAA), dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and noradrenaline were measured by high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) and 3-methoxy-4-hydroxyphenylethyl-eneglycol (MHPG) was measured by HPLC coupled with fluorimetric detection. Ratios 5-HIAA/5-HT, DOPAC + HVA/DA and MHPG/NA were taken as an index of serotonin, dopamine and noradrenaline turnovers, respectively. Tripelennamine (1 and 10 mg/kg) significantly reduced serotonin turnover in control and morphine-dependent mice, and potentiated the serotonin turnover reduction when it was administered 30 min before naloxone injection. The dopamine turnover was diminished by tripelennamine (1 and 10 mg/kg) in the morphine-dependent group. Tripelennamine (10 mg/kg) reduced noradrenaline turnover during abstinence. These results suggest that the potentiation of opiate abstinence by tripelennamine could be related to its antiserotonergic profile.     

Acute scopolamine treatment decreases dopamine metabolism in rat hippocampus and frontal cortex

The aim of the present study was to correlate the impairment of cognitive function induced by scopolamine with the activity of dopaminergic synapses in brain areas which are innervated by the mesocortical limbic system (e.g. hippocampus and frontal cortex) or by the mesostriatal system (e.g. striatum and nucleus accumbens). The results indicate that acetylcholine receptor blockade induced by the intraperitoneal injection of 0.5 mg/kg scopolamine resulted in a selective decrease in the content of the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This effect appeared to be specific for the hippocampus and frontal cortex. Indeed, dopamine turnover in striatum and nucleus accumbens was not affected by scopolamine treatment. The scopolamine-induced decrease of dopamine turnover in both hippocampus and frontal cortex paralleled in terms of both time- and dose-dependence the drug-induced amnesic effects, as measured by a passive avoidance behavioral test.     

Effect of repeated dietary exposure of aflatoxin B1 on brain biogenic amines and metabolites in the rat

Male Sprague-Dawley rats were treated po twice weekly for 3 weeks with a low (32.8 micrograms/kg) and high dose (327.9 micrograms/kg) of aflatoxin B1 (AFB1) in corn oil. A control group received corn oil only. At the end of the experiment the rats were killed, and the concentrations of the brain catecholamines, norepinephrine (NE) and dopamine (DA), catecholamine metabolites, 3-methoxy-4-hydroxymandelic acid (VMA), homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC), and the indoleamine serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were determined by high-pressure liquid chromatography in five brain regions. The major effects were found in striatal dopamine and serotonin concentrations, with decreases of 37 and 29%, respectively. A corresponding decline was observed in the dopamine metabolites, homovanillic acid (44%) and dihydroxyphenylacetic acid (30%). Concentrations of these neurotransmitters and metabolites were only marginally altered in cerebral cortex, cerebellum, hypothalamus, and medulla oblongata. It appears that a major effect of AFB1 is on dopaminergic pathways, possible by selectively perturbing the conversion of tyrosine to biogenic catecholamine neurotransmitters.