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PubMed1976

Effect of theophylline on monoamine metabolism in the rat brain.

The effect of theophylline on brain monoamine metabolism was studied in rats. Single doses of theophylline caused a striking and dose-related increase in the levels of 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MOPEG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain. The level of brain homovanillic acid was only slightly affected. No appreciable change occurred, however, in the levels of brain norepinephrine, serotonin and dopamine. The increased level of brain MOPEG-SO4 or 5-HIAA after theophylline does not appear to result from its interference with the transport system for the acids in the brain since the rate of decline of the acid levels following pargyline was not affected. Under the conditions of brain monoamine oxidase inhibition, theophylline enhanced the increase in brain normetanephrine level without causing any change in 3-methoxytyramine level. The enhancement of brain normetanephrine level by theophylline became more pronounced when rats were pretreated with imipramine in addition to pargyline. These results suggest that, in the brain, theophylline may cause a release of serotonin leading to its increased turnover. The results also confirm the previous conclusion that the methylxanthine causes a release of norepinephrine and a concomitant increase in its turnover in the brain.

3-Methoxy-4-hydroxyphenylethanol↗

PubMed1985

The effects of amiflamine on cerebrospinal fluid amine metabolites in the rhesus monkey.

Amiflamine, a drug reported to be a reversible inhibitor of monoamine oxidase type A (MAO-A) selective for serotonergic neurons in rodents, was administered to rhesus monkeys over a 12-fold dosage range (0.5-6 mg/kg). Amiflamine produced small, essentially equivalent reductions in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA, 1-28%), 3-methoxy-4-hydroxyphenylglycol (MHPG, 4-26%), and homovanillic acid (HVA, 7-29%), suggesting that the effects of amiflamine are approximately equal on serotonin, norepinephrine and dopamine metabolism in nonhuman primates. Concentrations of amiflamine were very low in CSF 3-6 h after drug administration (less than 7 nmol/l), while those of its two major, biologically active metabolites were higher (22-150 nmol/l) and varied in relative proportions among the monkeys. Further investigation is required of some preliminary observations of a possible association between drug metabolite variations and the substantial individual differences in the amine metabolite changes following amiflamine treatment. MAO-B in platelets was not inhibited by 6 mg/kg amiflamine, indicating that MAO-A selectivity was maintained. At low amiflamine doses, early and transient increases in CSF 5-HIAA and HVA concentrations were observed, suggesting an amine-releasing effect of the drug within brain serotonergic and dopaminergic neurons.

Animals↗

PubMed1985

Repetitive measurement of monoamine metabolite levels in cerebrospinal fluid of conscious rats: effects of reserpine and haloperidol.

A simple high performance liquid chromatographic method with electrochemical detection is described for the simultaneous determination of unconjugated 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the principal central nervous system (CNS) metabolites of noradrenaline, serotonin and dopamine (DA), respectively, in small samples of cisternal cerebrospinal fluid (CSF) obtained repeatedly from freely moving rats. Amounts of 30-50 microliter of CSF could be collected repeatedly every 30-60 min allowing monitoring of monoamine metabolite concentration levels in CSF under physiological conditions. None of the metabolites showed any clear diurnal variation. A single injection of reserpine caused a prominent elevation in the concentrations of MHPG, 5-HIAA and HVA in CSF. However, after a rapid increase, the concentration of MHPG was decreased by 85% from the control values. Haloperidol caused a 3-fold increase in the concentration of HVA, indicating increased DA turnover in the CNS. The method enables the reliable quantitative determination of three major monoamine metabolites in small samples of CSF from freely moving rats and appears to be a useful tool in the evaluation of the validity of the clinically used research methods of monitoring drug-induced alterations in CNS monoaminergic activity by metabolite measurements in CSF.

Animals↗

PubMed1986

Methylenedioxymethamphetamine: a potentially neurotoxic amphetamine analogue.

The amphetamine analogue, methylenedioxymethamphetamine (MDMA) has received considerable attention recently as a novel and increasingly popular psychoactive agent. When administered acutely to rats in high doses, MDMA caused a selective and dramatic decrease in brain concentrations of serotonin and its metabolite, 5-hydroxyindoleacetic acid. The depletion of serotonin and its metabolite persisted for up to at least one week after a single injection of MDMA at approximately four to five times the acute dose reported for humans. These results are discussed in terms of the possible neurotoxic effects of MDMA.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1986

The effects of desipramine, zimelidine, electroconvulsive treatment and lithium on rat brain biogenic amines: a comparison with peripheral changes.

The effects of 4 common treatments for affective disorders on total body norepinephrine (NE) and dopamine (DA) turnover and metabolism were evaluated in rats. The treatments were chronic desipramine (DMI), zimelidine (ZMI), electroconvulsion (ECT) and lithium (Li). The central effects of ECT and Li were also assessed in the brain. The results obtained were compared with the effects of these 4 treatments on total NE (Sum NE) and DA (Sum DA) turnover in depressed patients. We have also evaluated central and/or peripheral effects of these treatments on phenylethylamine, p-tyramine and serotonin metabolism. The urinary changes in Sum NE and DA observed after DMI, ZMI and Li in the rat were similar to those found in depressed patients; Sum NE was significantly reduced. In contrast to its effects on depressed patients, chronic ECT significantly increased Sum NE. Similar to depressed patients, ECT reduced the fraction of NE escaping re-uptake in the rat. Sum DA was not affected by DMI, ZMI or ECT, but was significantly reduced by chronic Li treatment. All 4 treatments significantly reduced serotonin metabolism as indicated by reduced 5-hydroxyindoleacetic acid excretion rates. DMI, ZMI and Li treatments significantly reduced phenylethylamine urinary but not p-tyramine urinary outputs. The opposite effect was observed after ECT. Consistent with their effects on Sum NE, Li reduced while ECT increased hypothalamic NE turnover as deduced from the changes in 3-methoxy-4-hydroxyphenylglycol's rate of formation. As for Sum DA, Li had no effect on 3,4-dihydroxyphenylacetic acid or homovanillic acid's rates of formation in the caudate nucleus. Chronic ECT produced a small, but significant increase in homovanillic acid's rate of formation in the caudate nucleus.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1986

Chronic imipramine administration reduces apomorphine inhibitory effects.

Changes in activity of dopaminergic and serotonergic systems were assessed after acute and chronic (14 days) imipramine (10 mg/kg) administration in mice. For this purpose, biochemical and behavioural tests were performed at different intervals of time after withdrawal of treatment. Brain levels of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, homovanillic acid and 3,4-dihydroxyphenylacetic acid were assayed by a fluorometric method. Locomotion and stationary behaviour were investigated in the open-field test. The results of the experiments suggest that chronic imipramine reduces the inhibitory effects of apomorphine upon the dopaminergic system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Differential effects of d-fenfluramine and p-chloroamphetamine on H75/12-induced depletion of 5-hydroxytryptamine and dopamine in the rat brain.

The effects of the two 5-HT-releasing drugs, p-chloroamphetamine and d-fenfluramine, on central serotoninergic and dopaminergic systems were compared in adult rats. Both drugs (0.5-5.0 mg/kg i.p., 2 hr before death) produced a dose-dependent reduction in levels of 5-HT, but only p-chloroamphetamine decreased the levels of 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus, striatum and cerebral cortex. Within the dose range tested, d-fenfluramine did not affect the levels of DA and of its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in brain. By contrast, p-chloroamphetamine significantly increased the levels of DA and HVA and decreased the levels of DOPAC, notably in the striatum. As expected of a 5-HT uptake inhibitor, d-fenfluramine at small doses (0.2-0.5 mg/kg) prevented the depletion of 5-HT due to 4-methyl-alpha-ethyl-meta-tyramine (H75/12, 40 mg/kg i.p.), whereas at large doses (1.0-5.0 mg/kg) d-fenfluramine, like p-chloroamphetamine (0.2-1.0 mg/kg), slightly enhanced the effect of H75/12. Neither d-fenfluramine (0.5 mg/kg) nor p-chloroamphetamine (0.5 mg/kg) affected the depletion of DA due to H75/12. These data indicate that p-chloroamphetamine is a 5-HT-releasing drug, at any dose between 0.2 and 5.0 mg/kg, whereas d-fenfluramine acts as a 5-HT uptake inhibitor at 0.2-0.5 mg/kg and as a 5-HT releasing drug at larger doses. On account of the potential neurotoxicity of 5-HT-releasing drugs but not 5-HT uptake inhibitors, it can be inferred that d-fenfluramine is very probably devoid of any neurotoxic action in the dose range (less than 1.0 mg/kg) required for its anorectic action.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

Neurochemical changes in pigeon cerebrospinal fluid during chronic administration of buspirone or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).

Cerebrospinal fluid (CSF), collected repeatedly from White Carneau pigeons chronically implanted with guide cannulae located in the lateral ventricles, was analyzed for metabolites of serotonin, dopamine and norepinephrine after acute and chronic administration of buspirone or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Following the acute administration of 3.0 mg/kg buspirone, levels of 5-hydroxyindoleacetic acid (5-HIAA) decreased, while increases occurred in the dopamine metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Decreases in 5-HIAA persisted throughout the chronic dosing regimen (36 days), while dopamine metabolites returned to control levels within 8 days. When chronic buspirone was discontinued, levels of 5-HIAA were restored to predrug control levels, while levels of HVA, DOPAC and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) decreased. All metabolites returned to predrug control levels within one week following buspirone discontinuation except for MHPG, which remained depressed. When the acute effects of buspirone were reexamined, levels of 5-HIAA were again significantly decreased, while HVA and DOPAC levels, as well as those of MHPG, increased significantly. Acute administration of the 5-HT1A receptor ligand 8-OH-DPAT (3.0 mg/kg) resulted in large decreases in 5-HIAA levels that persisted throughout the period of chronic administration. Neither acute nor daily administration of 8-OH-DPAT changed levels of HVA, DOPAC or MHPG. Large increases in 5-HIAA occurred when chronic 8-OH-DPAT was discontinued but declined within one week to control levels. Following a two-week drug-free period, 8-OH-DPAT again caused a significant reduction in 5-HIAA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Extracellular levels of serotonin in the medial pontine reticular formation in relation to sleep-wake cycle in cats: a microdialysis study.

Extracellular levels of endogenous serotonin (5-hydroxytryptamine; 5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were measured in the medial pontine reticular formation (medial PRF) of intact cats. A microdialysis probe was inserted through a guide cannula into the medial PRF. At least 12 h after the probe insertion, in vivo brain microdialysis was initiated. The perfusion rate was 1 microliters/min, and perfusate fractions at regular intervals of 20 min were collected. Changes in extracellular 5-HT levels were compared across sleep-wake states of the animals, such as waking (W), slow wave sleep (SWS) and rapid eye movement (REM) sleep. To assess sleep-wake states, EEG, EMG, EOG and PGO waves were simultaneously recorded in parallel with microdialysis of the medial PRF. Extracellular 5-HT levels were highest (20-28 fmol/20 microliters) during W. As the animals entered SWS, 5-HT levels decreased to about 90% of those during W. The state of REM sleep usually interrupted SWS for 3-8 min. During the longer periods of REM sleep, during the 20 min periods in which the perfusates were collected, we observed the lowest 5-HT levels (60-50%).

Animals↗

PubMed1984

Acute effects of toluene on circadian rhythms of sleep-wakefulness and brain monoamine metabolism in rats.

Acute effects of a single i.p. injection of toluene on circadian rhythms of sleep-wakefulness were investigated in rats which were chronically implanted with EEG and EMG electrodes for polygraphic recordings. The toluene injection produced an initial increase in wakefulness (W) and a subsequent increase in slow-wave sleep (SWS) during the dark period. In an attempt to clarify mechanisms of these biphasic effects of toluene on sleep-wakefulness rhythms, brain monoamines and their metabolites were determined at the times of the initial increase in W and the increased SWS. The initial increase in W was associated with an increase in cortical NA, MHPG and 5-HT together with a decrease in cortical 5-hydroxyindoleacetic acid (5-HIAA), while the increased SWS during the dark period was associated with an increase in 5-HIAA and a concomitant decrease in 3-methoxy-4-hydroxyphenylglycol (MHPG). The toluene-induced changes in sleep-wakefulness seemed to be manifested at lower blood levels of toluene than the behavioral signs of central nervous system (CNS) depression. These biphasic effects of toluene on circadian sleep-wakefulness rhythms are discussed in terms of the reciprocal interactions between central 5-HT and NA neurons.

Animals↗

PubMed1984

Changes in 5-HIAA and 5-HT levels in lumbar CSF following morphine administration to conscious dogs.

Monoamine metabolites in the lumbar cerebrospinal fluid were measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) in 6 conscious dogs after administration of morphine. The concentrations of dopamine and its metabolites exhibited only small variations whereas a significant increase in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) occurred after a latency of 5 min and culminated after 1 h. The increased release of 5-HT and 5-HIAA and behavioral changes (restlessness, sialorrhea) induced by morphine were prevented by administration of naloxone or nalorphine.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Fluoxetine increases the extracellular levels of serotonin in the nucleus accumbens.

The effects of an IP injection of the monoamine uptake inhibitor fluoxetine on the extracellular concentration of serotonin (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens of awake and freely moving rats were examined using a push-pull perfusion technique. Baseline values of 5-HT, 5-HIAA, DA, DOPAC and HVA in the perfusates were approximately 0.07, 13, 0.8, 49 and 12 pmol/hr, respectively. The IP administration of 5 and 10 mg/kg fluoxetine dose-dependently elevated the amounts of 5-HT 3- and 13-fold, respectively, in the push-pull perfusate, with the maximum reached within one hour after drug administration. Moreover, 10 mg/kg fluoxetine also significantly decreased the levels of 5-HIAA in the perfusate as much as 50% within 2-3 hours. On the other hand, no significant effect of 5 or 10 mg/kg fluoxetine was observed on the contents of DA, DOPAC and HVA in the push-pull perfusates. The data indicate that fluoxetine, in accord with its role as a 5-HT uptake inhibitor, increases the physiologically active pool of 5-HT in the nucleus accumbens under in vivo conditions.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Peripheral nerve stimulation increases serotonin and dopamine metabolites in rat spinal cord.

Extracellular serotonin (5-HT), dopamine (DA), and their metabolites, 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), were assessed in the rat lumbar spinal cord (L3-4) by in vivo microdialysis with high performance liquid chromatography and electrochemical detection (HPLC-ECD). Under urethane-chloralose anesthesia, basal levels of 5-HT and DA in the dialysates were approximately 1.0-1.2 pg/22 microliters sample, 5-HIAA, DOPAC, and HVA were constant at 322.6 +/- 14.9, 8.6 +/- 0.7, and 10.4 +/- 0.4 pg/22 microliters sample (mean +/- SE), respectively. Local application of 100 mM KCl via the dialysis probe increased the 5-HT and DA. Peripheral nerve stimulation that selectively excited the large (A-beta) or small (A-delta) myelinated fibres increased the metabolites. Excitation of the A-beta fibers increased the levels of 5-HIAA to 138%, DOPAC to 155%, and HVA to 143% of the controls. Stimulation of the A-delta fibers increased 5-HIAA to 121%, DOPAC to 120%, and HVA to 124% of the controls. The results suggest that non-nociceptive peripheral nerve stimulation may activate the descending 5-HT and DA systems in the spinal cord.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Oral administration of 3,4-methylenedioxymethamphetamine (MDMA) produces selective serotonergic depletion in the nonhuman primate.

MDMA (3,4-methylenedioxymethamphetamine) has been reported to produce serotonergic depletion in nonhuman primates at doses as low as 2.5 mg/kg (1-2 times the typical human dose). The current study evaluated the dose-response relationships of MDMA (1.25-20.0 mg/kg) using regional concentrations of serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and home cage behavior as endpoints. Adult female rhesus monkeys (n = 16) were treated orally with 0, 1.25, 2.5, or 20.0 mg/kg MDMA twice daily for 4 consecutive days. Eighteen behaviors were measured in the home cage prior to, during, and after MDMA treatment. One month after the last dose, the animals were sacrificed and brains dissected into several regions for neurochemical analyses. 5-HT and 5-HIAA were analyzed via HPLC/EC. The lower doses of MDMA (1.25 and 2.5 mg/kg) did not significantly alter 5-HT or 5-HIAA concentrations in any brain region except hippocampus in which 5-HT concentrations were decreased after 2.5 mg/kg. MDMA at 20.0 mg/kg significantly decreased 5-HT and 5-HIAA concentrations in several cortical and midbrain structures. However, 5-HT and 5-HIAA concentrations in brain stem and hypothalamus were not significantly altered after any dose of MDMA. Combined with previous data from this laboratory, these results indicate that the decreased concentrations of 5-HT and 5-HIAA in selected brain regions show a selective dose-response relationship for MDMA-induced neurotoxicity as measured by serotonergic depletion in the nonhuman primate.

3,4-Dihydroxyphenylacetic Acid↗

PubMedDate not supplied

Behavioral and neurochemical effects of chronic methylenedioxymethamphetamine (MDMA) treatment in rhesus monkeys.

Effects of chronic treatment with the putative serotonergic neurotoxicant MDMA were assessed in rhesus macaques using behavior in an operant test battery (OTB) designed to model aspects of time estimation, short-term memory, motivation, learning, and color and position discrimination. After an initial acute dose-response assessment, escalating doses of MDMA (0.10-20.0 mg/kg, im, twice daily, for 14 consecutive days at each dose) were administered, followed by three additional acute dose-response assessments. In general, tolerance to MDMA's acute effects was evident in all OTB tasks by the second week of repeated exposure to each individual MDMA dose and as doses escalated. Baseline OTB performance after chronic treatment was not significantly altered. Residual behavioral tolerance to MDMA's acute effects, however, was evident in all OTB tasks but was least pronounced in the motivation task. Monkeys were sacrificed (21 months after chronic treatment) and brains were dissected into several regions for neurochemical analyses. Serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were analyzed via HPLC. Although MDMA-treated monkeys tended to have lower 5-HT concentrations in the frontal cortex, chronic MDMA treatment had no significant effects on 5-HT concentrations in any brain area sampled. Hippocampal 5-HIAA concentration, 5-HT uptake sites, and turnover of 5-HT of MDMA-treated monkeys were significantly lower than control values. DA concentrations in the CN of MDMA-treated monkeys were significantly greater than control values. No significant effects on DA concentrations were noted in any other brain area sampled. The absence of significant decreases in 5-HT and the general increase in DA concentrations are dissimilar to neurochemical effects reported after a short course of MDMA treatment at relatively high doses. These data suggest that chronic administration of gradually increasing doses of MDMA results in long-lasting tolerance to the drugs acute effects on the complex brain functions modeled in the OTB. It is uncertain, however, if such tolerance is related to the observed decreases in uptake sites and turnover of 5-HT in the hippocampus of these monkeys.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Involvement of NMDA receptor mechanisms in the modulation of serotonin release in the lateral parabrachial nucleus in the rat.

Microdialysis was employed to investigate whether N-methyl-d-asparatate (NMDA) glutamate receptor mechanisms are involved in the modulation of serotonin (5-hydoxytryptamine, 5-HT) release in the region of the lateral parabrachial nucleus (LPBN) in freely moving rats. Perfusion of NMDA (10 and 50 microM) through the microdialysis probe significantly enhanced extracellular concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the LPBN area. Local perfusion of the NMDA antagonist dizocilpine (MK801, 10 and 50 microM) did not change the basal 5-HT and 5-HIAA levels in the LPBN area. MK801 (10 microM) administered together with NMDA antagonized the stimulant effect of NMDA (10 microM). The intake of 0.3M NaCl and water induced by subcutaneous injections of the diuretic furosemide (FURO, 10 mg/kg) and the angiotensin converting enzyme inhibitor captopril (CAP, 5 mg/kg) produced significant increases in the 5-HT and 5-HIAA concentrations in the LPBN area. The increased levels of 5-HT and 5-HIAA caused by the combined treatment with FURO and CAP were attenuated by perfusion of MK801 (10 microM). These results indicate the participation of NMDA receptors in the control of 5-HT release in the LPBN area.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Salivary prolactin as a marker for central serotonin turnover.

Central nervous system (CNS) serotonin deficits have been linked to many pathological behaviors in both human and nonhuman primates. The plasma prolactin response to fenfluramine has been widely used to assess CNS serotonin functioning in humans. Prolactin is also found as an integrated measure in saliva. We hypothesized that salivary prolactin concentrations would correlate positively with cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) in rhesus monkeys. Twenty-seven adult male and female rhesus macaques (Macaca mulatta) were sampled for concurrent saliva, blood, and CSF. Saliva and blood serum were assayed for prolactin concentrations, and CSF was assayed for 5-HIAA, homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). Salivary prolactin concentrations were positively correlated with CSF 5-HIAA concentrations. No other relationships between any of the measures, including that between salivary prolactin and serum prolactin, were found to be statistically significant. These findings suggest the possibility of using salivary prolactin concentrations as an index of CNS serotonin turnover in humans.

Animals↗

PubMed2000

Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain.

Islet amyloid polypeptide (IAPP or amylin) potently reduces food intake in rats at or near physiological concentrations. Although the mechanisms of action of IAPP are not understood, the brain is a suggested site. Changes in hypothalamic and striatal neurotransmission have been reported following acute systemic administration of a pharmacological concentration of IAPP. In the current study, we evaluated the effects of chronic administration of low doses of IAPP on satiety-related neurotransmitters and neuropeptides in the hypothalamus, hippocampus, striatum, left cortex, and right cortex of the rat. Doses of 0, 5 and 25 pmol IAPP/kg-min were administered subcutaneously for 2 or 5 days. Food intake was reduced by 27 and 44% (both P<0.001) for the 5 and 25 pmol/kg-min groups, respectively, in the 2-day experiment and was decreased by 14% (P<0.01) and 24% (P<0.001), respectively, in the 5-day experiment. Body weight was significantly decreased in a dose-dependent fashion. In the 2-day experiment, norepinephrine increased in the hypothalamus in the 5 pmol IAPP/kg-min group, and neurotensin increased in the hippocampus in the 25 pmol/kg-min rats (both P<0.05). In the 5-day, 5 pmol/kg-min rats, 5-hydroxyindoleacetic acid (5-HIAA) increased in the hypothalmus and cholecystokinin (CCK) increased in the striatum (both P<0.05). In the 5-day, 25 pmol/kg-min group, neuropeptide Y (NPY) increased in the hypothalamus (P<0.01) and CCK increased in the hypothalmus and striatum (both P<0.05). The present study confirms that IAPP is a potent anorectic peptide at low doses and suggests that IAPP not only affects classical neurotransmitters in the brain but also alters concentrations of neuropeptides known to be involved in food intake.

3,4-Dihydroxyphenylacetic Acid↗