Distribution of Free and Conjugated Dopamine in Human Caudate Nucleus, Hypothalamus, and Kidney

Abstract: The occurrence of free and conjugated dopamine was determined by HPLC in human caudate nucleus, hypothalamus, and kidney. Free norepinephrine and dihydroxyphenylacetic acid levels in some tissues were also determined. Conjugated dopamine was found to account for 25% of the total DA in the kidney. Conjugated DA accounted for 2.9% and 5.1% of the total DA in the caudate nucleus and hypothalamus, respectively. These results indicate that conjugated dopamine is not homogenously distributed in human tissue.     

Stress-Related Changes in Cerebral Catecholamine and Indoleamine Metabolism: Lack of Effect of Adrenalectomy and Corticosterone

The concentrations of catecholamine and indoleamine metabolites were measured in intact and adrenalectomized mice to determine whether adrenal hormones mediate or modulate the stress-induced responses. Thirty minutes of footshock resulted in significant increases of the ratios of the dopamine (DA) catabolite, dihydroxyphenylacetic acid (DOPAC), to DA in prefrontal cortex, nucleus accumbens, striatum, hypothalamus, and brainstem, and of homovanillic (HVA)/DA ratios in nucleus accumbens, striatum, amygdala, and hypothalamus. Ratios of 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine (NE) were also increased in prefrontal cortex, nucleus accumbens, septum, amygdala, hypothalamus, hippocampus, and brainstem. The concentration of NE was decreased in amygdala. 5-Hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT, serotonin) ratios and free tryptophan were also increased in every brain region. Very similar data were obtained from mice restrained for 30 min. Adrenalectomy resulted in increased HVA/DA ratios in prefrontal cortex and striatum, and 5-HIAA/5-HT in septum. The stress-related changes were largely similar in adrenalectomized mice. Significant interactions between adrenalectomy and footshock treatment occurred in prefrontal cortical DOPAC/DA and hypothalamic NE which was depleted only in adrenalectomized mice, suggesting tendencies for these measures to be more responsive in adrenalectomized mice. Corticosterone administration (0.5-2.0 mg/kg s.c.) which resulted in plasma concentrations in the physiological range did not alter the concentrations of the cerebral metabolites measured in any region. We conclude that adrenal hormones do not mediate cerebral catecholamine or indoleamine metabolism in stress, although adrenalectomy may affect HVA and 5-HIAA metabolism, and there was a tendency for catecholamines to be more sensitive to stress in adrenalectomized animals.     

Effect of eating bananas on plasma free and sulfate-conjugated catecholamines

The effect of eating bananas, a known and rich source of biogenic amines, on plasma free and sulfate-conjugated catecholamines was examined in normal human volunteers. Before ingestion conjugated norepinephrine (NE) and epinephrine (E) comprised 60% and 84% of the total concentration respectively. Free dopamine (DA) was undetectable. Although there was no change in free NE and E levels after eating bananas, free DA became measurable in some subjects. In contrast, conjugated NE and particularly DA, increased markedly in all subjects. More detailed study in 2 subjects indicated that this increase may persist for 8 hours after consumption. Available evidence suggests that sulfate conjugation of free catecholamines in banana largely takes place in the gut. It is important therefore to consider dietary influences when the physiological role of conjugated catecholamines. and perhaps free dopamine, is being assessed.     

Free, glucuronide, and sulfate catecholamines in the rat: effect of hypoxia

The formation and excretion of conjugated catecholamines (CA) was studied in conscious rats after sympathetic stimulation by hypoxia (5.5-6% O2, 4 h). Hypoxia induced a rapid and intense increase of free epinephrine (E, X 12) and norepinephrine (NE, X 6) but only a limited enhancement of free dopamine (DA, X 2). Sulfate conjugates of E and NE had kinetics similar to the free forms, while glucuronides were only moderately and lately altered. In contrast to free and sulfated DA, DA glucuronide, the major plasma conjugate, was decreased (-25%). This result suggests that DA glucuronide, unlike other CA conjugates, is not related to detoxication but might supply a CA precursor. Urinary conjugates badly reflected plasma conjugates. In normoxic controls, CA conjugates prevailed in the plasma, whereas the free amines prevailed in the urine. Hypoxia increased mainly the excretion of E and NE glucuronide but not of the free amines. Urinary DA, free or conjugated, was decreased (-25%), a result in keeping with plasma DA glucuronide only. The poor relations between plasma and urine catecholamines pinpoint the importance of the kidney in CA handling.     

Cocaine

Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice ip. Thirty minutes later, the brains were removed, and nine regions were isolated: olfactory bulbs, olfactory tubercles, prefrontal cortex, septum, striatum, amygdala, hypothalamus, hippocampus, and thalamus. Using high-performance liquid chromatography, concentrations of norepinephrine, dopamine, serotonin, and their major metabolites and the metabolite/neurotransmitter ratios were determined as an indicator of utilization. Serotonergic systems responded most dramatically. 5HIAA/5-HT decreases were seen in all the brain regions, except the septum, hippocampus, and olfactory bulbs. In most instances, the alterations were dose-dependent. The most profound changes were seen in the amygdala, prefrontal cortex, hypothalamus, and thalamus. For noradrenergic systems, significant responses were seen only in the amygdala, prefrontal cortex, and hypothalamus, but then only at the lower dose. The dopaminergic responses were more complex and not always dose-dependent. The DOPAC/DA ratio was decreased only in the amygdala and striatum at the lower dose, and the olfactory tubercles at the higher dose. It was increased in the septum. The HVA/DA ratios were decreased in the amygdala, prefrontal cortex, and hypothalamus, but only at the lower dose (like MHPG/NE). The 3MT/DA ratio was decreased in the thalamus at the lower dose and in the olfactory tubercles at the higher dose, whereas it was increased in the prefrontal cortex at the lower dose. The HVA and DOPAC routes of degradation were both utilized only by the amygdala. Thus, cocaine produced its most comprehensive effects in this nucleus, as well as the greatest absolute percentage changes for all three of the monoamine systems studied.     

Changes in catecholamine levels and turnover rates in hypothalamic,vocal control,and auditory nuclei in male zebra finches during development

The catecholamines norepinephrine (NE) and dopamine (DA) have been implicated in the sexual differentiation of brain and behavior and in species-specific learning in several species. To determine if these neurotransmitters might be involved in sexual differentiation of the vocal control system and song learning in male zebra finches, NE and DA levels and turnover rates were quantified in 10 behaviorally relevant brain nuclei [6 vocal control (VCN), 2 auditory (AN), and 2 hypothalamic (HN)] at four critical points during sexual differentiation of the VCN and the period of song learning, 25, 35, 55, and 90 days of age. Some birds were pretreated with α-methyl-para-tyrosine (αMPT) to allow estimation of NE and DA turnover rates. NE and DA levels in microdissected nuclei were quantified using high-performance liquid chromatography with electrochemical detection. αMPT treatment suppressed catecholamine synthesis just as effectively in juveniles as it does in adults and proved an effective method for estimating NE and DA turnover rates. Patterns of NE and DA function in most VCN and AN over development were quite different from those in HN in which NE and DA function changed gradually and showed no striking peaks. NE turnover rates changed significantly over development in all six VCN [nucleus interfacialis (Nlf), high vocal center (HVC), nucleus robustus of the archistriatum (RA), dorsomedial portion of the intercollicular nucleus (DM), Area X of the parolfactory lobe, and lateral portion of the magnocellular nucleus of the anterior neostriatum (IMAN)]; one AN [nucleus mesencephalicus lateralis pars dorsalis (MLd)], and one HN [preopticus anterior (POA)]. NE levels changed significantly in two VCN (Nlf and Area X). In Nlf, RA, Area X, IMAN, and MLd, NE levels and/or turnover rates showed a striking peak at day 25, which was not seen in HN. Both DA levels and turnover rates changed profoundly over development in 5 of 6 VCN (Nlf, RA, DM, Area X, and IMAN) and both AN (MLd and Field L). These nuclei showed striking peaks in DA levels and turnover rates, primarily on day 35 and/or 55, which then declined profoundly by day 90. This contrasted with the minimal change in DA turnover rates seen in one HN (POA) and the sixth VCN, HVC. In several VCN and AN, NE and DA levels and turnover rates during development reached levels never seen in adult males. Previous research has shown that catecholamine function is heightened in VCN during development compared to surrounding tissues. Our data demonstrate that NE and DA function during development shows pronounced peaks in most VCN not seen in HN. This is interesting because both VCN and HN are hormone sensitive, and both show hormone-modulated NE and DA function in adult males. The timing of these peaks suggests that increased catecholaminergic function may be involved in sexual differentiation of the VCN and song learning in finches. © 1998 John Wiley & Sons, Inc. J Neurobiol 34: 329–346, 1998     

Time-dependent changes in brain biogenic amine dynamics following castration in male rats

—Alterations in whole-brain and hypothalamic levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), dopamine (DA) as well as the turnover rates of NE and DA of adult male rats were analysed fluorometrically at either 3 weeks or 6 weeks following castration. Significant increases were observed in whole-brain (minus hypothalamus) 5-HIAA levels and hypothalamic DA levels, fractional rate constants and utilization rates at the 3 but not the 6 week intervals. Elevated levels of 5-HT were observed at both time intervals while an increase in whole-brain DA was seen only at the 6 week interval. Whole brain NE turnover rates of castrated animals did not differ significantly from those of sham-castrate control animals at either test interval. However, a tendency toward increased hypothalamic NE turnover rates was seen in the castrated animals. These biochemical changes resulted in decreased NE/5-HT and DA/5-HT ratios for the castrate rats as compared to controls. The results are discussed in relation to emotional and aggressive behavior and are interpreted as being consistent with the hypothesis purporting an inhibitory role for 5-HT and excitatory role for NE and DA in sex-specific behavior patterns including aggression.     

Electroacupuncture alters catecholamines in brain regions of rats

Electroacupuncture (EA) stimulation mediated the release of [³H]norepinephrine (NE) from synaptosomes prelabeled with [³H]NE. The pulse release of [³H]NE by EA stimulation was dependent on the presence of Ca²⁺. Treatment of rats with EA for 30 min at 4 Hz did not significantly alter the dopamine (DA) content in hypothalamus, cerebellum, pons, midbrain, and cerebral cortex regions, but the DA level was decreased by 20% in caudate nucleus. The NE level was found to increase by 43% in caudate nucleus and 38% in hypothalamus. The results indicate that only certain neuronal pathways are affected by the EA treatment, and that NE and DA may respond differently to such stimulation.     

Effect of psychotropic drugs on 3,4-dihydroxyphenylacetic acid (DOPAC) content in the medial basal hypothalamus

The effect of different psychotropic drugs on 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the medial basal hypothalamus has been studied by the use of a very sensitive radioenzymatic method. Apomorphine and haloperidol, which are known to respectively decrease and increase DOPAC levels in the caudate nucleus, fail to influence DOPAC level in the medial basal hypothalamus. Reserpine, which increases DOPAC level in the caudate nucleus, decreases it in the medial basal hypothalamus. Amphetamine decreases DOPAC level in the medial basal hypothalamus as it does in the caudate nucleus. These results suggest that DA metabolism in the medial basal hypothalamus is controlled by mechanisms different from those operating in other brain areas.     

Influence of hypo- and hyperthyroidism on the turnover rate of noradrenaline, dopamine and serotonin in various rat cerebral structures]

The effect of chronic treatment with tyroxine (T4) or propylthiouracile (PTU) on the turnover of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) has been studied in various areas of the rat brain (brain stem, hypothalamus, striatum and "rest of the brain"). The turnover of NE and DA was determined by the decay in endogenous levels after inhibition of tyrosine hydroxylase by alpha-methylparatyrosine and the turnover of 5-HT was evaluated by the initial accumulation of endogenous 5-HT after inhibition of monoamine oxydase by pargyline. T4 treatment accelerated the release of DA from the striatum but had no significant effects on NA release in the various cerebral areas : nevertheless the NE endogenous level was significantly reduced in the brain stem. PTU treatment delayed the release of DA and NA only from the "rest of the brain". Concerning 5-HT, the only significant variation was observed in the hypothalamus of PTU-treated rats and implied increased turnover. The possible relations between the changes in cerebral monoamines turnover and the behavioural alterations which are observed in thyroid disfunction are discussed.     

Circadian Fluctuation of Catecholamines in the Cockroach Brain-Subesophageal Ganglion Complex detected by HPLC-ECD

Fluctuations of catecholamine contents in the cockroach brain-subesophageal ganglion (Br-SG) complex were examined by HPLC with electrochemical detector. The chromatographic system detected dopamine (DA), norepinephrine (NE), epinephrine (EP) and some putative metabolites as standard compounds. Da, NE and EP were detected in the Br-SG complex whereas those metabolites such as 2,5-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy 4-hydroxy phenylglycol (MOPEG) were not detected from the tissue samples in a significant amount. The distribution of DA in the central nervous system was strongly biased toward cephalic ganglia, whereas EP was distributed more evenly over all ganglia. EP existed in both free and conjugated forms, the latter being predominant. Fluctuation patterns of these catecholamines were distinct; DA level kept constant throughout the day, at ca 200 ng/mg protein, NE showed a peak around AZT (artificial Zeitgeber time) 12, i.e., the light-off moment and the rhythm free-ran in constant darkness (DD), and both the free and the conjugated, i.e., acetylsulfate, forms of EP had peaks around mid-dark (AZT 18), in antiphase to the NE peak, and had a trough around AZT 12. Since both forms of EP showed the same fluctuation pattern, EP content in free form was regulated mainly by phenylethanolamine N -methyltransferase (PNMT) but not by hydrolysis of the conjugated EP. Since the enzymatic activities of monoamine oxidase (MAO), catechol O -methyltransferase (COMT) and aldehyde reductase (AR) were low, the fluctuation of these amines must be regulated by N -acetyltransferase (NAT), dopamine ß-hydroxylase (DBH) and PNMT.     

Effects of ethanol on brain monoamine content of spontaneously hypertensive rats (SHR)

Spontaneously hypertensive rats (SHR) were administered either 2.4 g/kg ethanol or an isocaloric glucose daily for 4 weeks and the levels of norepinephrine (NE), epinephrine (EP), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in different brain regions were determined. Results indicated a 3-fold increase in NE level in brain stem and hypothalamus and more than 2-fold increase in DA in corpus striatum in alcohol-treated rats as compared to controls. There was a significant increase in the level of DA in the corpus striatum but the levels in cerebral cortex, brain stem and hippocampus were decreased instead. Decreases in 5-HT levels were found in hypothalamus, brain stem, cortex and cerebellum of alcohol-treated brain as compared to untreated controls. These results indicate alterations of the biogenic amine contents in different regions of the SHR brain after chronic ethanol ingestion. Since stimulated release of biogenic amines in the SHR brain has been implicated in the regulation of blood pressure, changes due to ethanol ingestion may be a risk factor in hypertensive patients.     

Effect of cholecystokinin octapeptide sulphate ester on brain monoamines in the rat

The effect of different doses of intracerebro-ventricularly administered cholecystokinin octapeptide sulphate ester (CCK-8-SE) was studied on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus, mesencephalon, amygdala, septum and striatum, 10, 20 and 60 min following administration. The DA and NE content increased and the 5-HT content decreased in the hypothalamus and mesencephalon. A biphasic action was observed in the amygdala of DA, NE and 5-HT depending upon the time and doses used. Similar action was seen on DA and NE in the septum. In the striatum, the DA and 5-HT content decreased while the NE level first increased and then decreased. The data indicate that the CCK-8-SE is able to modify the activity of DA, NE and 5-HT in different brain regions in a time and dose-dependent manner, with a local specific action.     

ALTERATIONS IN THE TURNOVER OF BRAIN NOREPINEPHRINE AND DOPAMINE IN ALCOHOL-DEPENDENT RATS

Abstract— The turnover of brain norepinephrine (NE) and dopamine (DA) was studied in five groups of male Sprague-Dawley rats under different conditions of alcohol treatment: no treatment, acute treatment while intoxicated, acute treatment subsequent to elimination of alcohol from the blood, alcohol-dependence while still intoxicated and alcohol-dependence during a withdrawal syndrome. Turnover was determined from the rate of depletion of brain catecholamine levels after inhibition of tyrosine hydroxylase. In rats given a single dose of alcohol, NE turnover was increased, while DA turnover was unaffected during the few first hours after treatment. After that time the turnover of both NE and DA was reduced. In alcohol-dependent rats, whether intoxicated or undergoing a withdrawal syndrome, the turnover of NE was increased, while that of DA was decreased. These data suggest that catecholamines may mediate some of the symptoms of the alcohol withdrawal syndrome in the rat.     

Effects of l-DOPA on the Concentrations of Free and Sulfoconjugated Cathecholamines in Plasma, Cerebrospinal Fluid, Urine, and Central and Peripheral Nervous System Tissues of the Rat

The effects of subcutaneous injection of L-beta-3,4-dihydroxyphenylalamine (L-DOPA) on the concentrations of the catecholamines and catecholamine sulfates in the central and peripheral nervous systems of the rat were studied. The results showed that free 3,4-dihydroxyphenylethylamine (DA, dopamine) increased rapidly and markedly in the hypothalamus and striatum after L-DOPA but DA sulfate did not change. Increased concentrations of DA sulfate were detected in the CSF and in the plasma, where it reached a concentration of 130.8 +/- 12.8 ng/ml at 2 h, seven times the level of free DA (19.1 +/- 2.9 ng/ml). In the kidney the ratio of DA sulfate to free DA was reversed in favor of free DA. Urine samples of L-DOPA-treated rats showed a higher increase of free DA than DA sulfate, but free norepinephrine (NE) and NE sulfate remained unchanged. Concentrations of free DA and free NE in the adrenal glands of L-DOPA-treated rats showed no change. Adrenal DA sulfate and NE sulfate were not detectable in the control and L-DOPA-treated rats, suggesting that the adrenal glands lack the capacity to take up or store catecholamines and their sulfate counterparts from the plasma.     

The effect of ascorbic acid on plasma sulfate conjugated catecholamines after eating bananas

The effects of eating bananas, a rich source of biogenic amines, on the plasma concentration of free and sulfate conjugated norepinephrine (NE) and dopamine (DA), and free epinephrine (E), were examined in normal male subjects before and after treatment with ascorbic acid, 2 g daily for 7 days. There were no significant changes in the levels of free NE or E in any subjects after eating a banana, either before or after ascorbic acid. Plasma free DA became detectable in some subjects, but the overall changes were not significant. Sulfate conjugated DA and NE increased markedly after banana ingestion, as previously demonstrated in our laboratory. After ascorbic acid treatment the rise in sulphate conjugated NE was attenuated, presumably because ascorbic acid acts as a competitive inhibitor of sulfate conjugation. In contrast, the rise in conjugated DA was potentiated after ascorbic acid treatment. This may be indicative of the higher affinity of DA for phenolsulfotransferase, an inhibitory effect of ascorbic acid on dopamine-receptor coupling or of ascorbic acid protecting DA from oxidation in the gut.     

Corticotropin-Releasing Factor Stimulates Catecholamine Release in Hypothalamus and Prefrontal Cortex in Freely Moving Rats as Assessed by Microdialysis

Abstract: In vivo microdialysis was used to measure changes in extracellular concentrations of catecholamines and indoleamines in freely moving rats in response to administration of corticotropin-releasing factor (CRF). Dialysis probes were placed stereotaxically in either the medial hypothalamus or the medial prefrontal cortex. We used a repeated-measures design in which each rat received artificial CSF or one dose of CRF 3–4 h apart, and each subject was retested with the same treatments in the reverse order 5–7 days later. With the dialysis probe in the hypothalamus, intracerebroventricular administration of CRF (17 or 330 pmol) dose-dependently increased dialysate concentrations of norepinephrine (NE), dopamine (DA), and all their measurable catabolites except normetanephrine. The effects on NE were substantially greater than those on DA. Dialysate concentrations of serotonin could not be measured reliably, but those of its catabolite, 5-hydroxyindoleacetic acid, were also elevated. Concentrations of NE and DA were elevated within the first one or two (20 min) collection periods, with a peak response at ∼ 1–2 h. Dialysate concentrations of catecholamines and metabolites normally returned to baseline within 3 h. Similar data were obtained with dialysis probes in the medial prefrontal cortex after intracerebroventricular administration of 17 or 167 pmol of CRF, except that the increases in DA exceeded those of NE in this region. Intraperitoneal administration of CRF (1 nmol) similarly elevated dialysate concentrations of NE, DA, 5-hydroxyindoleacetic acid, and all catecholamine catabolites except normetanephrine in both medial hypothalamus and medial prefrontal cortex. These results support earlier neurochemical data suggesting that CRF administered both centrally and peripherally stimulates the release of both DA and NE in the brain.     

Concurrent Determination of Brain Dopamine and 5-Hydroxytryptamine Turnovers in Individual Freely Moving Rats Using Repeated Sampling of Cerebrospinal Fluid

5-Hydroxytryptamine (5-HT) turnover and dopamine (DA) turnover values were obtained in individual conscious rats by measuring the rates of accumulation of 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in cisternal CSF samples taken from each rat at 0, 30, and 60 min after probenecid (200 mg/kg i.p.) administration. In a separate experiment, 5-HT and DA turnover values were determined in CSF, striatum, and rest of brain of groups of rats killed 0, 30, or 60 min after probenecid. Whole brain turnover values were calculated from striatal and rest of brain values. Mean turnover values using CSF were comparable with both procedures. DA turnover values were greater when based on total (i.e., free + conjugated) DA metabolites than when based on free metabolites. After partial inhibition of monoamine synthesis with the decarboxylase inhibitor DL-alpha- monofluoromethyl -DOPA ( MFMD , 100 mg/kg p.o.) DA and 5-HT turnover values were comparably reduced in whole brain, rest of brain, and CSF but more markedly reduced in the striatum. Mean DA and 5-HT turnover values obtained using CSF were similar with probenecid doses over the range 150-250 mg/kg i.p. but were variable when repeatedly determined in the same rats after administration of 200 mg/kg probenecid. Results in general show that the CSF procedure may be used to determine concurrently both 5-HT and DA turnover (when estimated from the sum of total but not free metabolites) and that it provides a good index of whole brain turnover of these transmitters in the conscious individual rat.     

Neurochemical studies on Indian Hypericum perforatum L

The effect of acute administration of 50% standardised ethanolic extract of Indian Hypericum perforatum (IHp) was studied on the rat brain concentrations of monoamines and their metabolites in five different brain regions, viz. hypothalamus, hippocampus, striatum, pons-medulla and frontal cortex by a HPLC technique. IHp extract was administered at the doses of 50 and 200 mg/kg, p.o. and the brain monoamines were assayed after 30 min of the treatment. IHp treatment significantly decreased the levels of serotonin (5-HT) and its metabolite 5-hydroxy indole acetic acid (5-HIAA) and 5-HT turnover in all the brain regions assayed. On the other hand, IHp treatment significantly augmented the levels of norepinephrine (NE) and its metabolite methylhydroxy phenyl glycol (MHPG) and NE turnover in all the brain regions studied. Similarly, the levels of dopamine (DA) were also significantly augmented in the hypothalamus, striatum and frontal cortex. Likewise, the levels of dihydroxyphenyl acetic acid (DOPAC), the major metabolite of DA, were also increased in these brain areas. Pharmacological studies with IHp extract have shown two major behavioural actions, namely, anxiolytic and antidepressant effects. The present findings tend to rationalise these observations, reduced 5-HT activity being consonant with anxiolytic and increased NA and DA activity being consonant with antidepressant action.     

Circadian rhythms in catecholamine metabolites and cyclic nucleotide production

Circadian rhythms in noradrenergic (NE) and dopaminergic (DA) metabolites and in cyclic nucleotide production were measured in discrete regions of rat brain. A circadian rhythm was found in the concentration of the NE metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), in the hippocampus. No MHPG rhythm was found in frontal, cingulate, parietal, piriform, insular or temporal cortex, or in hypothalamus. Circadian rhythms in the concentration of the NE metabolite, 3,4-dihydroxyphenylglycol (DHPG), occurred in occipital and parietal cortex and hypothalamus, with no rhythm observable in temporal or insular cortex, hippocampus, pons-medulla or cerebellum. The 24-hr mean concentration of MHPG varied 3.5-fold, highest in cingulate and lowest in parietal, temporal and occipital cortex. The 24-hr mean concentration of DHPG varied 6-fold, highest in hypothalamus and lowest in parietal cortex. Circadian rhythms in the concentration of the DA metabolite, homovanillic acid (HVA), were found in olfactory tubercle, amygdala and caudate-putamen, but not in nucleus accumbens. A circadian rhythm in the concentration of the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), occurred in nucleus accumbens, but not in olfactory tubercle or caudate-putamen. The mean 24-hr concentration of HVA was highest in caudate-putamen, intermediate in nucleus accumbens, and lowest in olfactory tubercle and amygdala. The mean 24-hr concentration of DOPAC was highest in nucleus accumbens and lower in olfactory tubercle and caudate-putamen. Circadian rhythms were found in the concentration of cyclic GMP (cGMP) in all regions measured except parietal cortex. The mean 24-hr concentration varied 128-fold, highest in nucleus accumbens, frontal poles, and hypothalamus and lowest in cingulate cortex. Circadian rhythms in cyclic AMP (cAMP) concentration were found in piriform, temporal, occipital, cingulate, and parietal cortex, amygdala and nucleus accumbens. No rhythms were found in frontal or insular cortex, hypothalamus, hippocampus, caudate-putamen or olfactory tubercle. The 24-hr mean cAMP concentration varied 4-fold, highest in parietal cortex and lowest in caudate-putamen and amygdala. Norepinephrine metabolites and dopamine metabolites were rhythmic in few regions. It is, therefore, unlikely that the rhythmicity measured in adrenergic receptors is, in general, a response to rhythmic changes in adrenergic transmitter release. The putative second messenger response systems, especially cGMP, were more often rhythmic. The rhythms in cGMP are parallel in form and region to those in the alpha 1-adrenergic receptor and may act as 2nd messenger for that receptor.(ABSTRACT TRUNCATED AT 400 WORDS)