5-hydroxyindoleacetic Acid Concentrations Research Articles

PKC-α mediated alterations of indoleamine contents in diabetic rat brain

We previously have reported that acute or chronic diabetes in animals resulted in altered neurotransmitter levels. In this study, we investigated the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete areas of brain viz. striatum (ST), hippocampus (HC), hypothalamus (HT), midbrain (MB), pons medulla (PM), cerebellum (CB) and cerebral cortex (CCX) of control, untreated diabetic and insulin treated diabetic rats after 30 days. Alloxan (45 mg/kg) diabetic untreated rats, which showed hyperglycemia (>250 mg%), revealed significant increases of 5-HT level in ST, MB, PM, CB and CCX and the 5-HIAA level found to be increased significantly in ST, HC and MB. Whereas the insulin treated rats, which was maintained under normal glucose level (80–110 mg%), showed no significant changes in any of the areas studied. The expressions of PKC-α studied by immunoblotting also showed significant changes in ST, HC, MB, PM, CB and CCX that is identical to the changes of both 5-HT and 5-HIAA under similar condition, suggesting that the PKC-α may regulate the synthesis and release of indoleamines in diabetic animals.

Difficulties in establishing reference intervals for special fluids: the example of 5-hydroxyindoleacetic acid and homovanillic acid in cerebrospinal fluid.

Biochemical measurements in "special fluids" are complicated with the problem of reference intervals. Reference intervals are difficult to establish for these types of samples since they are usually only collected in patients with clinical suspicion of disease. Determination of neurotransmitter metabolites in cerebrospinal fluid illustrates this difficulty. This paper will review the factors and circumstances that have been identified or are suspected to modify the concentration of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid. In addition to obvious parameters such as age-related variation that can affect the concentration of 5-HIAA and HVA in cerebrospinal fluid, a variety of other factors can explain the wide range of "control" group sizes reported in the literature. Reference intervals must take into account the purpose of cerebrospinal fluid examinations, whether they be prospective studies to explore physio-pathologic relationships or for diagnostic purposes. In the latter case, certain neurological disorders cannot be excluded if a single measured value is within the reference interval.

Alterations in Regional Brain Neurotransmitters by Silymarin, a Natural Antioxidant Flavonoid Mixture, in BALB/c Mice

Silymarin, a natural antioxidant flavonoid mixture, exerts anti-inflammatory effects in the liver and hinders tumor formation. The effect of this flavonoid mixture on the central nervous system is unknown, although antioxidants are considered beneficial. Brain amines and metabolites were studied after a short-term silymarin treatment. BALB/c mice were intraperitoneally treated with 0, 10, 50, or 250 mg/kg of silymarin per day for 5 days. High-performance liquid chromatography coupled with electrochemical detection was performed to determine concentrations of norepinephrine (NE), dopamine (DA), dioxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT, serotonin) and 5-hydroxyindoleacetic acid (5-HIAA) in discrete brain regions. Analyses showed increased 5-HT levels in the cortex and increased DA and NE levels in the cerebellum in the highest dose group. Results indicated lack of general adverse effect on the brain amine metabolism and suggest that silymarin may have marginal serotonergic, dopaminergic, and noradrenergic effects.

IDRD2 TaqIA polymorphism is associated with urinary homovanillic acid levels in a sample of Spanish male alcoholic patients.

The TaqIA1 allele of the dopamine receptor gene D2 (DRD2) has been associated with alcoholism, as well as with other addictive behaviours. The exact nature of how the presence of this allele can be a vulnerability factor in the development of alcoholism remains unclear. In this study we found that the presence in the DRD2 genotype of the TaqIA1 allele in Spanish alcoholics is associated with higher levels of urine homovanillic acid (HVA) when compared to patients homozygous for the TaqIA2 allele. A sample of 142 Spanish male alcoholic patients was split into 2 groups on the basis of the presence or absence of the A1 allele in their genotype. The urine sample was analyzed by high performance liquid cromatography (HPLC), and the concentration of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and vanilylmandelic acid (VMA) was determined. We found a statistical difference in the concentration of HVA between the groups, that suggests this polymorphism could be related to the variance of urine HVA levels.

Transcription factor AP-2beta genotype, striatal dopamine D2 receptor density and cerebrospinal fluid monoamine metabolite concentrations in humans.

Transcription factor AP-2beta has been suggested to influence brain monoaminergic systems by regulating target genes. In order to explore a possible functional role, AP-2beta genotype was analysed in relation to striatal dopamine D2 receptor density determined in vivo by positron emission tomography in human subjects (n = 52). The AP-2beta genotype was also analysed in relation to cerebrospinal fluid (CSF) concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) in healthy human subjects (n = 90). There was no association between the AP-2beta genotype and measures of dopamine receptor density, or CSF 5-HIAA concentrations. However, AP-2beta genotype was associated with CSF-levels of HVA (in women) and MHPG. These data may suggest a functional involvement of AP-2beta in the dopaminergic system, but should be interpreted with caution until replicated.

Cerebrospinal fluid analysis differentiates multiple system atrophy from Parkinson's disease.

We investigated whether cerebrospinal fluid (CSF) analysis discriminates between idiopathic Parkinson's disease (PD; n = 35) and multiple system atrophy (MSA; n = 30). The median CSF concentration of the neurotransmitter metabolites 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) was reduced significantly (49-70%) in MSA compared to PD. In contrast, several brain-specific proteins (tau, neuron-specific enolase, myelin basic protein) were elevated (130-230%) in MSA compared with those in PD. A combination of CSF tau and MHPG discriminated PD from MSA (adjusted odds ratios: tau, 27.2; MHPG, 0.14). Our data suggest that the more progressive and widespread neurodegenerative nature of MSA, as compared with PD, is reflected in the composition of CSF. We propose that CSF analysis may become part of the diagnostic work-up of patients with parkinsonian syndromes.

Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain neurotransmitter levels without concurrent inhibition of the brain sphingolipid biosynthesis in mice

Myriocin is a specific serine palmitoyltransferase (SPT) inhibitor whose effect on the brain is unknown. Brain amine metabolism and sphingolipid biosynthesis were studied in mice treated intraperitoneally with 0, 0.1, 0.3 or 1 mg/kg per day of myriocin for 5 days. Regional concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT, serotonin), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE), were determined. Sphinganine (Sa) and sphingosine (So) concentrations and SPT activity in brain and liver were used to evaluate the impact of myriocin on sphingolipid biosynthesis. Myriocin treatment increased DA in striatum and hippocampus and reduced it in cortex. NE concentration decreased in cerebellum and 5-HT levels were reduced in cortex and in medulla oblongata. Changes in ratios for DOPAC/DA and HVA/DA were observed in hippocampus, cortex and midbrain. Brain Sa, So and SPT activity remained unchanged, whereas Sa and SPT activity decreased in liver. Results showed that myriocin may alter the levels and metabolism of brain amines and this effect is not related with inhibition of sphingolipid biosynthesis in the nervous system.

In vivo effects of aripiprazole on cortical and striatal dopaminergic and serotonergic function

In vivo microdialysis was used to monitor the effects of oral aripiprazole and olanzapine on basal extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) in the medial prefrontal cortex and striatum of conscious, freely moving rats. Acute aripiprazole administration did not affect dopamine output, but produced moderate increases in DOPAC and HVA concentrations, in medial prefrontal cortex or striatum of drug-naı̈ve rats. Similarly, aripiprazole did not affect dopamine output but produced moderate elevations in DOPAC and HVA concentrations in the striatum of chronic aripiprazole-pretreated rats. Olanzapine produced comparatively larger elevations in dopamine, DOPAC, and HVA in both regions, which, in the striatum, were diminished after chronic olanzapine exposure. Aripiprazole reduced extracellular 5-HIAA concentrations in the medial prefrontal cortex and striatum of drug-naı̈ve rats, but not in chronic aripiprazole-pretreated rats. Together, these data provide in vivo evidence of aripiprazole-induced changes in forebrain dopaminergic and serotonergic function that may reflect its partial agonist activity at presynaptic dopamine D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors.

The effect of neurotoxic doses of methamphetamine on methamphetamine-conditioned place preference in rats.

Methamphetamine has been shown to produce neurotoxicity demonstrated by depletions of dopamine and serotonin in the striatum and nucleus accumbens. The current study examined the effects of neurotoxic doses of methamphetamine on the rewarding effect of subsequent administration of methamphetamine assessed by the conditioned place preference (CPP) procedure. Male and female rats were treated with a neurotoxic regimen of methamphetamine (4 x 10 mg/kg, s.c., once every 2 h) or saline, and concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid were measured 15 days later in the striatum, nucleus accumbens, and prefrontal cortex (PFC). In another experiment, male rats were given methamphetamine neurotoxic treatment or saline and were then conditioned 7 days later with methamphetamine (0.1, 0.3, or 1.0 mg/kg, s.c.) or saline using a four-trial CPP procedure. Locomotor activity was also measured during the conditioning sessions to investigate whether or not the neurotoxic methamphetamine treatment altered locomotor activity following a subsequent methamphetamine challenge. Males and females did not differ significantly in the amount of neurochemical depletion produced by methamphetamine in any brain region. Collapsed across sex, dopamine was significantly depleted in nucleus accumbens (25%) and striatum (51%); serotonin was significantly depleted in nucleus accumbens (35%), striatum (34%) and PFC (33%). The methamphetamine challenge dose dependently increased locomotor activity, but the increase was not affected by treatment with neurotoxic doses of methamphetamine. In contrast, treatment with neurotoxic doses of methamphetamine enhanced CPP at the intermediate conditioning dose (0.3 mg/kg). These results indicate that the rewarding effect of methamphetamine is enhanced by prior treatment with neurotoxic doses of methamphetamine, suggesting either a compensatory hyperfunctioning of spared dopamine neurons or a loss of inhibitory control from serotonergic input.

Postoperative nausea and vomiting in regional anesthesia: a review.

ANESTHESIA has become remarkably safe, and while death and permanent damage have become rare occurrences, other sequelae of anesthesia are gaining more importance. Postoperative nausea and vomiting (PONV) still is the most troublesome adverse event encountered in the recovery room, despite advances in prevention and treatment. The incidence of PONV has remained high and has a major negative impact on patient satisfaction about the overall surgical experience. Furthermore, the ongoing trend toward ambulatory procedures has increased the focus on PONV as its occurrence may delay discharge or cause unanticipated hospital admission. General anesthesia has long been considered as causing a greater frequency and severity of PONV than regional anesthetic techniques. Recent studies investigating this time-honored dictum in a controlled manner mostly, but not unanimously, confirmed it. Accordingly, considerable effort has been invested to examine etiology, define patients at risk, and outline preventive and therapeutic strategies in patients undergoing general anesthesia. Reviews dealing with PONV have discussed almost exclusively general anesthesia and largely ignored regional anesthesia. This contrasts with the increasing popularity of regional anesthesia. A survey in Europe showed that one third of patients are undergoing regional anesthesia for their operative procedure. In France, the proportion of regional anesthesia increased from 15 to 25% of all anesthetics administered from 1980 to 1996. The number of local anesthetic and analgesic agents available for regional anesthesia has increased over the last two decades. Since the introduction of intrathecal and epidural morphine in 1979, a multitude of medications, such as synthetic opioids, 2-agonists, and cholinesterase inhibitors, have been introduced in an attempt to enhance the action of local anesthetics. The decision about their usefulness will not only rely on their effects on nerve blockade and pain relief, but also on their influence on side effects such as PONV. This review focuses on PONV in the setting of perioperative regional anesthesia. General aspects of PONV, such as physiology, patient, and perioperative factors involved are discussed. Few studies regarding these issues have been specifically devoted to regional anesthesia. Therefore, much information must be derived from investigations of general anesthesia. Specific regional anesthetic techniques and the influence of adjunctive medications on PONV are also presented. Combined general–regional anesthesia is purposefully excluded, avoiding the many variables introduced by general anesthesia. A final section is devoted to continuous peripheral nerve blocks and their possible impact on PONV.

Physiological correlates of aggression and impulsivity in free-ranging female primates.

We examined the relations among cerebrospinal fluid (CSF) monoamine metabolite concentrations, plasma hormone concentrations, aggression, and impulsive risk-taking behavior in a free-ranging population of female rhesus macaques. We selected 44 juvenile female rhesus macaques as subjects from a population of approximately 3000 macaques that inhabit a 475-acre Sea Island. We obtained CSF and blood samples, and recorded behavioral observations over a subsequent 18-month period. Our results indicate an inverse correlation between CSF concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), and the frequency of low-intensity restrained aggression typically associated with matrilineal defense of social status. In contrast, previous research with males has shown an inverse correlation between CSF 5-HIAA concentrations and levels of violent unstrained aggression typically associated with traumatic injury and death. We also noted a negative correlation between plasma concentrations of the stress hormone cortisol and the frequency of low-intensity aggressive acts, a finding not reported in our previous studies with males. Further examination revealed a negative correlation between CSF 5-HIAA concentrations and the rate of long dangerous leaps through the forest canopy, suggesting that the relation between low serotonergic functioning and impulsivity may generalize to both female and male primates. These results indicate that females with low CSF 5-HIAA concentrations, like their male counterparts, are at increased risk for impulsive temperament, but that unlike males, females may be buffered from this risk through intersexual differences in life history patterns and social affiliation.

The effect of tryptophan deficiency in the brain on rat fatigue levels: a rat model of fatigue reduction.

The level of tryptophan and 5-hydroxyindoleacetic acid were measured in the brain (striatum) of rats on tryptophan-deficient diet and tryptophan-enriched diet. We measured concentrations of tryptophan and 5-hydroxyindoleacetic acid in striatum by using microdialysis and HPLC methods. The extracellular level of tryptophan and 5-hydroxyindoleacetic acid concentration in the striatum of a tryptophan-reduced rats was decreased by about 50% compared with a tryptophan-enriched diet. In the tryptophan-reduced condition, the rats an increased the running time of more than 100 min, compared with those on a tryptophan-enriched diet. These results suggest the tryptophan and 5-hydroxytryptamine in the central nervous system are involved in fatigue.

Anatomical and functional evidence for a stress-responsive, monoamine-accumulating area in the dorsomedial hypothalamus of adult rat brain

The dorsomedial hypothalamus (DMH) plays an important role in relaying information to neural pathways mediating neuroendocrine, autonomic, and behavioral responses to stress. Evidence suggests that the DMH is a structurally and functionally diverse integrative structure that contributes to both facilitation and inhibition of the hypothalamo–pituitary–adrenal axis, depending on the nature of the stimulus and the specific neural circuits involved. Previous studies have determined that stress or stress-related stimuli elevate tissue concentrations of serotonin (5-hydroxytryptamine; 5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine, and noradrenaline selectively within the DMH. In order to determine the specific region of the rat DMH involved, we used high-performance liquid chromatography with electrochemical detection to measure tissue concentrations of 5-HT, 5-HIAA, dopamine, and noradrenaline within five different subregions of the DMH in adult female Lewis and Fischer rats immediately or 4 h following a 30-min period of restraint stress. Compared to unrestrained control rats, restrained rats had elevated concentrations of 5-HT, 5-HIAA, dopamine, and noradrenaline immediately after a 30-min period of restraint and had elevated concentrations of 5-HT 4 h following the onset of a 30-min period of restraint stress. These effects were confined to a specific region that included medial portions of the dorsal hypothalamic area and dorsal ependymal, subependymal, and neuronal components of the periventricular nucleus. Furthermore, these effects were observed in Lewis rats, but not Fischer rats, two closely related rat strains with well-documented differences in neurochemical, neuroendocrine, autonomic, and behavioral responses to stress. These data provide support for the existence of a stress-responsive, amine-accumulating area in the DMH that may play an important role in the differential stress responsiveness of Lewis and Fischer rats.

Left-handedness is Correlated with CSF Monoamine Metabolite and Plasma Cortisol Concentrations, and with Impaired Sociality, in Free-ranging Adult Male Rhesus Macaques (Macaca mulatta)

In this research we examined biological and behavioural correlates of handedness in free-ranging adult male rhesus macaques (Macaca mulatta). Specifically, we examined relationships between handedness and cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma concentrations of the hormones cortisol and adrenocorticotropin (ACTH), and multiple indices of social behaviour, including occurrences of proximity to other animals, grooming, submission, and aggression. We determined handedness through systematic observation of animals reaching for food in their unrestricted home environment. The frequency of right- versus left-hand use was significantly positively correlated with CSF 5-HIAA, CSF MHPG, and plasma cortisol concentrations, and with social proximity and the frequency and duration of bouts in which animals received grooming. The frequency of right- versus left-hand use was significantly negatively correlated with the frequency of submissive behaviour, and with the frequency and intensity of bouts in which animals received aggression. We conclude that handedness is associated with an array of biological and behavioural processes in free-ranging adult male rhesus macaques and that left-handedness may be used to identify individuals at increased risk for impaired functioning of the serotonin, norepinephrine, and hypothalamic-pituitary-adrenal systems, and for social isolation and susceptibility to violent attack.

DMXAA: An antivascular agent with multiple host responses

Purpose: To measure host responses to the antivascular agent DMXAA (5,6-dimethylxanthenone-4-acetic acid) and to compare them with those of other antivascular agents.Methods: Induction of tumor necrosis was measured in s.c. murine Colon 38 carcinomas growing in normal or tumor necrosis factor (TNF) receptor-1 knockout mice. Plasma and tumor tissue TNF concentrations were measured by ELISA. Plasma concentrations of 5-hydroxyindoleacetic acid (as a measure of serotonin release) and nitrite (as a measure of nitric oxide release) were measured by high-performance liquid chromatography.Results: Administration of DMXAA to tumor-bearing mice increased plasma and tumor tissue-associated TNF, in addition to increasing plasma nitric oxide, distinguishing its action from that of mitotic poisons that had an antivascular action. Results from TNF receptor-1 knockout mice showed that TNF played an important role in both its antitumor action and its host toxicity. Release of serotonin occurred in response to mitotic poisons, as well as to DMXAA.Conclusions: The antivascular action of DMXAA involves in situ production in tumor tissue of a cascade of vasoactive events, including a direct effect on vascular endothelial cells and indirect vascular effects involving TNF, other cytokines, serotonin, and nitric oxide. Now that Phase I clinical trials of DMXAA are completed, the optimization of this cascade in cancer patients is a major challenge. Plasma 5-hydroxyindoleacetic acid concentrations may provide a useful surrogate marker for the antivascular effects of DMXAA and other antivascular agents.

Self-rated childhood emotional neglect and CSF monoamine indices in abstinent cocaine-abusing adults: possible implications for suicidal behavior

Non-human primate studies suggest that early environmental influences may have an enduring effect on central serotonin function. Therefore, it was decided to examine in humans whether childhood trauma might be related to cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) as an adult. A total of 29 withdrawn cocaine-dependent patients completed the Childhood Trauma Questionnaire. They also had a lumbar puncture for determination of CSF concentrations of 5-HIAA. CSF concentrations of the dopamine metabolite homovanillic acid (HVA) were also determined. Childhood emotional neglect scores showed significant negative correlations with CSF levels of 5-HIAA and HVA, and patients with emotional neglect scores above the median had significantly lower CSF 5-HIAA and HVA levels than patients with emotional neglect scores at or below the median. These findings suggest the possibility that childhood trauma may have an effect on central monoamine function as an adult.

Vasopressin in CSF and plasma in depressed suicide attempters: preliminary results

Increased plasma arginine vasopressin (AVP) concentrations have been reported in depressed suicide attempters. Plasma AVP is primarily produced by the magnocellular system in response to increased plasma osmolality, and central AVP may be independently regulated. In the present study we investigated cerebrospinal fluid (CSF) and plasma AVP concentrations in depressed patients and controls. Nineteen drug-free depressed psychiatric inpatients (nine suicide attempters) and nine neurological control subjects underwent lumbar puncture and psychiatric evaluation. CSF and plasma concentrations of AVP, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and cortisol were assayed. In 15 depressed patients (eight suicide attempters), the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test was performed to examine the hypothalamic–pituitary–adrenocortical (HPA) system. There were no differences between depressed subjects and controls in all parameters measured. Suicide attempters did not differ from nonattempters. In depressed patients, plasma AVP correlated positively with cortisol. There was no relationship between CSF AVP and monoamine metabolites in CSF.

Effects of pentylenetetrazol-induced kindling of seizures on rat emotional behavior and brain monoaminergic systems

The influence of pentylenetetrazol (PTZ)-induced kindling of seizures on the rat emotional behavior, the brain monoamine turnover rate measured in vitro, and correlation between behavioral and biochemical parameters, were examined in rats. The repeated administration of PTZ (35 mg/kg, ip) evoked kindled seizures in rats (Stage 4 or 5 of clonic–tonic convulsions—maximum). PTZ kindling caused selective changes in the rat emotional behavior, present in some models of anxiety only (a decreased freezing time in the conditioned freezing test and a decreased spontaneous and aversively conditioned ultrasonic vocalization). Simultaneously, PTZ kindling decreased the concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the prefrontal cortex, decreased the DA (HVA/DA ratio) turnover rate in the striatum, and inhibited the serotonin (5-HT) metabolism (5-HIAA/5-HT ratio) in the hippocampus and the prefrontal cortex. Correlations between dopamine (DA) or 5-HT regional metabolic rates in brain structures and animal behavior were either abolished or reversed in PTZ-kindled animals. It is concluded that both DA and 5-HT systems contribute to the emotional effects of PTZ-induced kindling of seizures. The hypothesis is put forward that PTZ kindling-induced inhibition of the serotonergic innervation may lead to the compensatory increase in 5-HT 1A receptors in the dentate gyrus of the hippocampus, thus evoking the anxiolytic-like changes in animal behavior.

Suicide.

Suicide is a multidimensional concomitant of psychiatric diagnoses, especially mood disorders, and is complex in both its causation and in the treatment of those at risk. It has known risk and protective factors that tend to be fairly consistent worldwide, with some cultural variation. Even with standardised assessment and prediction scales (such as the Hamilton or Beck depression inventories), suicide prediction results in about 30% false positives. The most common biological marker of suicide is reduced concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid in the CSF of suicide cases versus controls. Although suicide prevention is ideally primary, in fact most treatment is secondary or tertiary. Dependent on the individual characteristics present, suicide prevention usually includes a pharmacological cocktail (especially one of the selective serotonin reuptake inhibitors, to raise serotonin concentrations, perhaps combined with an anxiolytic, mood stabilising, or antipsychotic agent), supportive psychotherapy (often cognitive or behavioural therapy), and sometimes electroconvulsive therapy. Perceived danger to self can necessitate treatment in hospital.

Serotonin, testosterone and alcohol in the etiology of domestic violence

In a previous study we administered the panicogenic agent sodium lactate to a select group of perpetrators of domestic violence and comparison groups. Results of that study showed that perpetrators exhibited exaggerated lactate-induced fear, panic and rage. In this current study, we compared the cerebral spinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and testosterone obtained from perpetrators of domestic violence and a group of healthy comparison subjects. All subjects were assessed for DSM-III-R diagnoses. Perpetrators with alcohol dependence (DV-ALC) ( n=13), perpetrators without alcohol dependence (DV-NALC) ( n=10) and healthy comparison subjects (HCS) ( n=20) were clinically assessed using the Spielberger Trait Anxiety, Brown–Goodwin Aggression Scale, Buss Durkee Hostility Inventory and Straus Conflict Tactics. Following an overnight fast and bed rest, subjects received a lumbar puncture to obtain CSF concentrations of 5-HIAA and testosterone. Perpetrators scored significantly higher on measures of aggression than HCS. DV-NALC had significantly lower concentrations of CSF 5-HIAA and higher Straus Conflict Tactics (CT) physical violence scores than DV-ALC and HCS. DV-ALC had significantly higher concentrations of CSF testosterone than DV-NALC. DV-ALC also had significantly higher Straus CT physical violence scores than HCS. DV-NALC and DV-ALC differed on 5-HIAA concentrations, testosterone concentrations, Straus CT physical violence scores and alcohol dependence. These results suggest that DV-NALC and DV-ALC groups could have different biological mechanisms mediating domestic violence.