束缚加悬吊应激模型大鼠不同脑区组织单胺类神经递质的变化

目的研究束缚加悬吊应激对大鼠不同脑区组织单胺类神经递质的影响。方法束缚加悬吊应激6h后,荧光法测定不同脑区单胺类神经递质去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)含量。结果与正常组比较,小脑、间脑5-HT、5-HIAA含量明显下降(均P<0.01)),间脑NE含量明显升高(P<0.01);而大脑、脑干NE、DA、5-HT、5-HIAA无明显变化。结论不同脑区对束缚加悬吊应激的反应性不同,间脑5-HT的下降可能与抑郁症有关。     

柴胡疏肝散对肝气郁结证大鼠海马及下丘脑单胺类神经递质的影响

目的研究柴胡疏肝散对肝郁证大鼠行为学和大鼠海马及下丘脑单胺类神经递质的影响。方法用慢性束缚应激结合孤养法建立肝郁证大鼠模型,测评开野、蔗糖水实验,采用高效液相色谱法测定大鼠海马及下丘脑单胺类神经递质。结果模型组大鼠的行为学发生了明显变化,海马及下丘脑中5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、多巴胺(DA)含量均下降,去甲肾上腺素(NE)含量呈增加趋势,而柴胡疏肝散能调控其变化趋势。结论柴胡疏肝散能改善肝郁证大鼠行为学的变化,具有治疗肝郁证的作用,其作用机制可能与其能够调节肝郁证大鼠脑5-HT、5-HIAA、NE、DA有关,从而有效发挥抗肝郁作用。     

固真方对老年大鼠海马和下丘脑单胺类神经递质含量的影响

观察补肾益精方药固真方对老年大鼠海马和下丘脑单胺类神经递质(NE、DA和5-HT)含量影响的结果表明:老年大鼠海马NE、5-HT含量以及下丘脑NE、DA和5-HT含量显著低于青年对照组;而固真方能明显提高老年大鼠海马下降的NE以及下丘脑下降的NE、DA和5-HT含量,但对海马5-HT作用不明显。由此推测,固真方具有部分纠正老年大鼠中枢单胺类神经递质紊乱作用,从而延缓老年大鼠神经内分泌-免疫网的老化,提高胸腺依赖性免疫功能。     

氯胺酮对束缚加悬吊应激大鼠脑组织单胺类神经递质的影响

目的 观察麻醉剂氯胺酮(ketamine)对束缚加悬吊应激大鼠脑组织不同脑区单胺类神经递质去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)含量的影响.方法 30只雄性SD大鼠随机分成3组,束缚加悬吊应激对照组(S组),非应激氯胺酮组(k1组),束缚加悬吊应激氯胺酮(10 mg/kg)组(k2组),输液后6 h,断头处死所有大鼠,取脑组织,荧光法测定不同脑区单胺类神经递质NE、DA、5-HT含量.结果 氯胺酮麻醉组脑干、皮质NE明显降低,小脑的NE明显升高;脑干、皮质DA明显升高,小脑的DA无明显变化;而小脑氯胺酮麻醉组5-HT明显降低,脑干和皮质无明显变化.结论 氯胺酮对应激大鼠脑组织不同脑区单胺类神经递质含量有不同的影响,5-HT的降低,NE、DA的升高可能与抑郁有关.     

开心散对SAMP8小鼠神经递质的影响

目的观察开心散对快速老化痴呆模型小鼠SAMP8神经递质的影响。方法将40只SAMP8小鼠按随机数字表法分为模型组、开心散高剂量组、开心散低剂量组、艾地苯醌组,每组10只,选10只SAMR1小鼠为正常组。灌胃给药干预8 w后,取血浆及组织上清,采用酶联免疫吸附法检测小鼠脑组织及血浆5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)、去甲肾上腺素(NE)、多巴胺(DA)含量。结果与正常组比较,各组脑组织5-HT、5-HIAA、NE、DA含量显著降低(P<0.01),血浆5-HT、5-HIAA、NE、DA含量显著升高(P<0.01);与模型组比较,开心散高剂量组和低剂量组脑组织5-HT、5-HIAA、NE、DA含量显著升高(P<0.01),血浆5-HT、5-HIAA、NE、DA含量显著降低(P<0.01)。结论开心散可以通过改善快速老化痴呆模型小鼠单胺类神经递质的含量,调整神经递质的不平衡状态,进而改善阿尔茨海默病(AD)的行为和精神症状。     

束缚加悬吊应激大鼠脑组织单胺类神经递质的变化及异丙酚对其的影响

目的 研究麻醉剂异丙酚对束缚加悬吊应激大鼠脑组织不同脑区单胺类神经递质去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)含量的影响.方法 30只雄性SD大鼠随机分成3组,束缚加悬吊应激对照组(S组),小剂量异丙酚(5mg/kg)组(p1组),大剂量异丙酚( 10 mg/kg)组(p2组),输液后6h,断头处死所有大鼠,取脑组织,荧光法测定不同脑区单胺类神经递质NE、DA、5-HT含量.结果 小剂量异丙酚组脑干、小脑组织中5 -HT明显降低,小脑组织中的NE明显升高;大剂量异丙酚组脑干、小脑组织中DA明显升高,小脑组织中的NE明显升高.结论 异丙酚对应激大鼠脑组织不同脑区单胺类神经递质含量有不同的影响,5-HT的降低,NE、DA的升高可能与高血压有关.     

敦煌石室大宝胶囊对衰老大鼠脑组织单胺类神经递质的影响

目的 观察敦煌石室大宝胶囊(DHDB)对衰老模型大鼠脑组织单胺类神经递质去甲肾上腺素(NE)、多巴胺(DA) 和5-羟色胺(5-HT)含量的影响.方法 采用D-半乳糖建立大鼠衰老模型,测定大脑皮层内的NE、DA和5-HT含量.结果 模型组大鼠脑组织内NE、DA、5-HT含量与空白组比较均有明显降低(P<0.05),应用DHDB治疗后,治疗组大鼠脑组织内NE、DA、5-HT含量均显著增高(P<0.05).结论 DHDB可提高衰老模型动物脑组织单胺类神经递质的含量,对改善大脑功能有一定的作用.     

实验性甲状腺功能低下大鼠下丘脑神经递质的变化及其对TSH分泌的调节

本文目的在于探讨甲状腺低功大鼠下丘脑神经递质的变化及其对血清 TSH 水平的影响。结果表明:低甲大鼠下丘脑神经递质的代谢比较活跃,NE 及5-HIAA 较对照组增高;下丘脑 NE、5-HIAA、5-HIAA/5-HT 与血清 TSH 呈线性正相关,NE 与 T_4,5-HIAA 与 T_3、T_4均呈线性负相关。由此推测,NE 及5-HT 系统能够促进 TSH 的分泌和释放。甲状腺激素对腺垂体 TSH的负反馈调节作用可能由两方面的参与,其一是甲状腺激素对腺垂体 TSH 的直接负反馈调节作用,其二是甲状腺激素可能通过神经递质的改变发挥其对 TSH 的负反馈调节作用。     

高碘暴露对甲状腺功能减退症患者机体内单胺类神经递质代谢的影响

目的分析研究健康群体和甲状腺功能减退症患者外周血中单胺类神经递质的含量差异,探讨高碘暴露对甲状腺功能减退症患者机体内单胺类神经递质代谢的影响。方法抽取高碘地区30例甲状腺功能减退症患者作为观察组,另选取30例体检健康者作为对照组,检测两组血浆中5-羟吲哚乙酸(5-HIAA)、5-羟色胺(5-HT)、血液中多巴胺(DA)含量。结果观察组5-HIAA、5-HT、DA含量均明显高于对照组,差异有统计学意义(P0.05);5-HT/5-HIAA比值组间比较差异无统计学意义(P0.05);5-HT水平和血浆FT3含量呈正相关性(r=0.878,P=0.001),5-HIAA水平和尿碘浓度(UIC)呈正相关性(r=0.372,P=0.31);在对照组中,5-HT水平与血浆FT3含量呈负相关性(r=-0.728,P=0.013),与尿碘浓度呈负相关性(r=-0.635,P=0.006),与FT4含量呈正相关性(r=0.618,P=0.039)。结论高碘暴露可对甲状腺功能减退症患者机体中单胺类神经递质代谢状态产生重要影响,破坏下丘脑-垂体-甲状腺轴正常功能,对患者生命健康构成严重威胁。     

雌激素对抑郁大鼠海马单胺类神经递质含量的影响及缰核在其中的作用

目的 探讨雌激素对抑郁大鼠海马内单胺类递质含量的调节以及缰核在其中的作用.方法 雌性Wistar大鼠随机被分成6组:正常对照组( Control)、抑郁模型组(Depression)、假手术组(SHAM)、去卵巢组(OVX)、雌二醇组(OV/ER)、缰核损毁组(Hb lesion).用高效液相色谱法( HPLC)检测各组海马内5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)递质的含量.结果 OVX组大鼠海马内5-HT、NE和DA含量与SHAM组大鼠相比降低,OV/ER组大鼠海马内5-HT、NE和DA含量与OVX组大鼠相比均显著回升.Depression组大鼠海马内5-HT、NE和DA含量与Control组相比明显降低;抑郁大鼠外侧缰核损毁后,海马内的5-HT、NE和DA含量均升高.结论 缰核可以通过对海马功能的影响介导雌激素改善抑郁行为的作用.     

N-acetyl cysteine reverses social isolation rearing induced changes in cortico-striatal monoamines in rats

Schizophrenia is causally associated with early-life environmental stress, implicating oxidative stress in its pathophysiology. N-acetyl cysteine (NAC), a glutathione precursor and antioxidant, is emerging as a useful agent in the adjunctive treatment of schizophrenia and other psychiatric illnesses. However, its actions on brain monoamine metabolism are unknown. Social isolation rearing (SIR) in rats presents with face, predictive and construct validity for schizophrenia. This study evaluated the dose-dependent effects of NAC (50, 150 and 250 mg/kg/day × 14 days) on SIR- vs. socially reared induced changes in cortico-striatal levels of dopamine (DA), serotonin (5-HT) noradrenaline (NA) and their associated metabolites. SIR induced significant deficits in frontal cortical DA and its metabolites, 3,4-dihydroxyphenylacetic acid (Dopac) and homovanillic acid (HVA), reduced 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and reduced levels of the NA metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG). In addition, significant elevations in frontal cortical NA and striatal DA, Dopac, HVA, 5-HT, 5-HIAA, NA and MHPG were also observed in SIR rats. NAC at 150 and 250 mg/kg reversed all cortico-striatal DA, Dopac, HVA, 5-HT, 5-HIAA and striatal NA alterations in SIR animals, with 250 mg/kg of NAC also reversing alterations in cortico-striatal MHPG. In conclusion, SIR profoundly alters cortico-striatal DA, 5-HT and NA pathways that parallel observations in schizophrenia, while these changes are dose-dependently reversed or abrogated by sub-chronic NAC treatment. A modulatory action on cortico-striatal monoamines may explain NACs’ therapeutic use in schizophrenia and possibly other psychiatric disorders, where redox dysfunction or oxidative stress is a causal factor.     

Changes in brain monoamine metabolism in rats with acute ischemic hepatic failure under artificial cardiopulmonary management.

A study was conducted to investigate changes in monoamine metabolism in the brain of rats with acute ischemic hepatic failure (AHF) induced by two-stage hepatic devascularization. Strict artificial cardiopulmonary management was used to exclude possible confounding effects of hypotension, hypothermia and hypoxemia that often appear in AHF. Rats were put in an incubator at 34 degrees C before the ligation of the hepatic artery (second stage operation), tracheotomized and ventilated artificially throughout the remaining experimental periods. No significant difference was observed in physiological parameters, including body temperature, pulse rate and systolic arterial blood pressure or PaO2 between AHF and sham operated rats. Brain levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), and serotonin (5-hydroxytryptamine, 5HT) and its metabolite 5-hydroxyindoleacetic acid (5HIAA) were determined by HPLC-voltametry. AHF rats showed significantly higher MHPG, DOPAC, 5HIAA and lower NE levels in the brain compared to controls. In addition, a significant negative correlation between NE and tyrosine (Tyr), a significant positive correlation between MHPG and Tyr or phenylalanine (Phe), and a significant positive correlation between DOPAC and Tyr or Phe were observed. In conclusion, the changes in monoamine metabolism in the brain of AHF rats are clearly induced specifically by hepatic failure itself, possibly through an altered metabolism of amino acids.     

Effects of cyclic hydrostatic pressure on the brain biogenic amines concentrations in the flounder, Platichthys flesus

The present study evaluated the effects of cyclic variations of hydrostatic pressure (HP) on neurotransmitters in the whole brain of flounder. The concentrations of the biogenic amines L-3,4-dihydroxyphenylalanine (L-DOPA), dopamine (DA), norepinephrine (NE), epinephrine (E), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), 5-hydroxytryptamine (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) were measured. Fish were subjected to HP cyclic variations which mimic naturally occurring conditions for a period of 14 days. DA, NE and 5-HT concentrations were significantly smaller by 21, 24 and 36%, respectively, compared to control fish. The concentrations of monoamine metabolites HVA, 3-MT and 5-HIAA were also smaller than those in control fish. These results suggest that central monoaminergic systems were influenced during long exposure to cyclic HP. The decreases of central neurotransmitters content might be involved in the physiological and behavioral responses to intermittent HP in fish.     

Effects of idebenone on monoamine metabolites in cerebrospinal fluid of patients with cerebrovascular dementia

Monoamine metabolites and norepinephrine (NE) in the cerebrospinal fluid of patients with cerebrovascular dementia were measured to study the effects of administration of idebenone. Six patients with cerebral infarction and one with cerebral hemorrhage (mean age 65.4 years) were enrolled as subjects. All the patients had mental and intelligence impairment which was evaluated by the Hasegawa's Dementia Rating (DR) Scale. The patients were medicated with a 90 mg/day dose of idebenone for 1 to 2 months, and homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and NE in the cerebrospinal fluid were determined by high-performance liquid chromatography before and after the medication of idebenone. Before the medication, the level of HVA was 21.7 +/- 1.4 ng/ml (mean +/- SE), which was significantly lower (p less than 0.01) as compared with that in control subjects of similar age. The level of 5-HIAA was 18.5 +/- 2.7 ng/ml, and that of MHPG 9.5 +/- 0.7 ng/ml, both of which were lower than those of the controls, though statistically not significant. NE was similar to the control value. After administration of idebenone, HVA measured was 27.1 +/- 3.2 ng/ml, showing a tendency to increase. The levels of 5-HIAA and MHPG were 26.7 +/- 2.3 ng/ml and 10.7 +/- 0.6 ng/ml, respectively, which were significantly (p less than 0.05) higher than the premedication values. The percentages of the change were 12.8 +/- 8.0 for HVA, 58.2 +/- 18.5 for 5-HIAA and 14.2 +/- 5.0 for MHPG. The score of the DR scale was improved by 5 or less after the idebenone medication in most subjects. HVA and 5-HIAA increased markedly in the patients who showed a tendency of improvement of mental impairment as evaluated by the DR scale. The results suggested that idebenone would improve abnormalities in neurotransmitters of patients with cerebrovascular dementia, especially promoting serotonin turnover.     

Neurotransmitter metabolites in CSF: an external quality control scheme

We report an international external quality control scheme on neurotransmitter metabolites in cerebrospinal fluid (CSF). The neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are analysed to diagnose inborn errors of neurotransmitter metabolism. HVA is the catabolite of dopamine; 5-HIAA is the catabolite of serotonin; and MHPG is the catabolite of noradrenaline. In the first phase, 12 laboratories from six countries participated in this special quality control scheme to define the present state of the art and achieve harmonization in analytical outcome and interpretation. In the second part, recoveries, dilutions and methods for sample preparation were compared. The results of 3 of 12 laboratories were excluded because of unacceptable intralaboratory coefficients of variations (CV) for HVA and/or 5-HIAA. The inter- and intralaboratory CVs, the linearity and the recovery were acceptable for the other laboratories for both parameters.Unacceptable differences in the reference ranges between laboratories, leading to differences in interpretation of the results, became obvious. There was a significant improvement of the interlaboratory CV for HVA after standardization with a calibrator. The reproducibility of MHPG measurement appeared to be adequately established in only two laboratories and recovery was low in all five measuring this metabolite. The quality control scheme is an invaluable tool for controlling the analytical outcome and providing support to laboratories to improve their quality.     

A Nonhuman Primate Model of Type II Alcoholism? Part 2. Diminished Social Competence and Excessive Aggression Correlates with Low Cerebrospinal Fluid 5-Hydroxyindoleacetic Acid Concentrations

The purpose of this study was to develop an animal model for behavioral features of type II, early-onset alcohol abuse. To perform this research, cerebrospinal fluid (CSF) monoamine metabolite concentrations and home-cage social behaviors of 29 rhesus macaque subjects were examined in a 4-year longitudinal study. Half of the monkeys were reared for their first 6 months with their mothers, and the other half were reared without adults, instead with access only to monkeys of similar age. When the subjects were 6 months old, and again when they were 50 months old, they underwent a series of four, 4-day social separations. We obtained cisternal CSF before and during the first and last separation of each series to quantify 5-hydroxy-indoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylgycol (MHPG), and homovanillic acid concentrations. After the 6-month separations, subjects were placed into social groups, and social dominance rankings were assessed. Before and after the 50-month separations, social dominance rankings were evaluated again, and home-cage aggression and social behavior data were collected. Over the 3 1/2 years between CSF samplings, records were maintained of subjects' removal from their social groups for excessive aggression or treatment for wounding. Our results showed that among infants, reduced CSF 5-HIAA was correlated with low social dominance. As young adults, subjects from both rearing groups with low CSF 5-HIAA and MHPG concentrations exhibited reduced rates of social interaction and low social dominance rankings. In addition, peer-reared subjects with low CSF 5-HIAA concentrations exhibited inept social behaviors, and were frequently removed from their social groups for excessive aggression and deviant social behaviors. From these results, we conclude that the peer-rearing paradigm aggravates the untoward social consequences associated with low CSF 5-HIAA concentrations over and beyond reducing CSF 5-HIAA concentrations, suggesting that early experiences may contribute to CNS serotonin changes that increase the disposition to type II-related behaviors.     

Circadian rhythms of dopamine, glutamate and GABA in the striatum and nucleus accumbens of the awake rat: modulation by light

Using microdialysis, we investigated the circadian rhythms of the extracellular concentrations of dopamine, glutamate and gamma-aminobutyric acid (GABA) in the striatum and nucleus accumbens of the awake rat. Wistar rats were maintained in a 12 hr dark:12 hr light (12:12) cycle for 2 wk before the experiment began. The neurotransmitter levels were measured every 30 min for 30 hr in control (maintaining the 12:12 cycle) or in experimental conditions under a 24-h light period (continuous light) or under a 24-h dark interval (continuous dark). The dopamine metabolites, DOPAC and HVA, and the main serotonin metabolite, 5-HIAA, were measured along with arginine and glutamine under all conditions. In 12:12 conditions, a circadian rhythm of dopamine, glutamate and GABA was found in both the striatum and nucleus accumbens. Again under 12:12 conditions, DOPAC, HVA, 5-HIAA, and arginine, but not glutamine, fluctuated in a circadian rhythm. In the striatum under constant light conditions, there was a circadian rhythm of dopamine, glutamate, GABA, DOPAC and HVA, but not 5-HIAA. By contrast, when the rats were kept under continuous dark, dopamine and its metabolites, DOPAC and HVA (but not glutamate and GABA), did not fluctuate in a circadian rhythm. In the nucleus accumbens, under both constant light or dark conditions, no changes were found in the circadian rhythm in any of the neurotransmitters and metabolites studied. These findings show that in the striatum, dopamine but not glutamate and GABA, seem to be influenced by light. In the nucleus accumbens, however, the three neurotransmitters had a circadian rhythm, which was independent of light.     

High concentrations of epinephrine derived from a central source and of 5-hydroxyindole-3-acetic acid in hypophysial portal plasma

This study was designed to determine if active secretion of epinephrine (EPI) and/or 5-hydroxytryptamine (5-HT) from the hypothalamus into the hypophysial portal vasculature takes place, in addition to the well-known secretion of dopamine (DA). Hypophysial portal plasma was collected from urethane-anesthetized male rats by stalk cannulation (Porter method) or by periodic aspiration of portal blood (Worthington and Fink method). Portal and peripheral plasma concentrations of EPI, 5-HT, DA and 5-hydroxyindole-3-acetic acid (5-HIAA) were concurrently measured by high performance liquid chromatography with electrochemical detection. Significantly higher concentrations of EPI were found in hypophysial portal than in peripheral plasma. After adrenalectomy (ADX), peripheral plasma levels of EPI were undetectable, whereas portal plasma EPI levels were only slightly attenuated. Although 5-HT levels in portal and peripheral plasma were not different, 5-HIAA levels were 3-fold higher in portal plasma. DA was 10-15 fold higher in portal plasma. All the above differences were found independent of the collection method. The high level of 5-HIAA in portal plasma was not due to conversion of 5-HT to 5-HIAA by monoamine oxidase in plasma. The results indicate that in addition to DA, another amine (EPI) and an amine metabolite (5-HIAA) have a concentration gradient in portal vs peripheral plasma. Moreover, the presence of EPI in portal plasma after ADX is a strong indication that EPI is primarily derived from a central source, suggesting that the amine may have a direct physiological role in the regulation of anterior pituitary function.     

Endogenous opioid peptide modulation of LH secretion in the ewe lamb: possible involvement of 5-hydroxytryptamine

Evidence from several species suggest that the endogenous opioid peptides participate in the regulation of gonadotrophin and prolactin secretion. The aim of the present study involving intact and ovariectomized prepubertal ewe lambs was to compare the effects in vivo of an opioid peptide agonist [D-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33-824) and antagonist, naloxone, on concentrations of LH and prolactin in plasma, and levels of neurotransmitter metabolites in cerebrospinal fluid (CSF), with their effects in vitro on the release of gonadotrophin-releasing hormone (GnRH) and neurotransmitters from isolated median eminences. Infusion of FK 33-824 (0.5 mg/30 min) in vivo depressed plasma LH levels in both intact and ovariectomized lambs; this effect could be reversed by naloxone. In ovariectomized lambs, the inhibitory action of FK 33-824 on plasma LH levels was associated with a 13% rise in the concentration of the metabolite of 5-hydroxytryptamine, 5-hydroxyindolacetic acid (5-HIAA). Concurrent administration of naloxone resulted in an abrupt 33% fall in CSF levels of 5-HIAA. No significant changes in plasma concentrations of prolactin or CSF concentrations of the metabolites of dopamine were observed in response to the administration of FK 33-824 or FK 33-824 plus naloxone. That FK 33-824 inhibited LH release through a central mechanism was confirmed using superfused median eminences in vitro. Thus FK 33-824 (1 mumol/l) greatly diminished the release of GnRH induced by the introduction of a depolarizing stimulus (36 mmol K+/l) in tissue obtained from both intact and ovariectomized ewe lambs.(ABSTRACT TRUNCATED AT 250 WORDS)     

A Nonhuman Primate Model of Type II Excessive Alcohol Consumption? Part 1. Low Cerebrospinal Fluid 5-Hydroxyindoleacetic Acid Concentrations and Diminished Social Competence Correlate with Excessive Alcohol Consumption

Developmental, biochemical, and behavioral concomitants of excessive alcohol consumption were investigated using a nonhuman primate model. The variables of interest were: (1) interindividual stability of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) from infancy to adulthood, (2) effect of parental deprivation early in life on adult CSF 5-HIAA concentrations; (3) correlations between CSF 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations and alcohol consumption; and (4) correlation between the frequency of competent social behaviors and alcohol consumption. Twenty-nine rhesus macaques were reared for their first 6 months either with their mothers or without adults in peer-only conditions. At 6 and 50 months of age, each subject underwent a series of four, 4-day social separations. Cisternal CSF was sampled before and during the first and last separations; concomitantly, observational data were collected on social dominance behavior in the home-cage. When they reached 50 months of age, the monkeys were provided free access to a palatable alcohol solution daily for 1-hr periods before, during, and after the social separations. Before and after the 50-month separations, data were collected on all types of social behavior in the home-cage. Results showed that peer-reared subjects consumed more alcohol than mother-reared subjects during baseline conditions. Mother-reared subjects, however, increased their rates of consumption to equal peer-reared subjects' rates of consumption during the conditions of a social separation stressor. Peer-reared subjects also exhibited lower CSF 5-HIAA concentrations in infancy and adulthood than their mother-reared counterparts. With rearing condition held constant, interindividual differences in CSF 5-HIAA, MHPG, and homovanillic acid were stable from infancy to adulthood, and high rates of alcohol were consumed by the young adult monkeys with low CSF 5-HIAA and MHPG concentrations, particularly when the CSF was obtained during the social separations. High rates of alcohol consumption were also observed in subjects with infrequent social interactions and less competent social behaviors. In contrast to the human data, we found no gender differences in rates of alcohol consumption, nor in the correlations between alcohol consumption and the other variables. With some exceptions, findings from the study are generally consistent with predictions from Cloninger's type II model of excessive alcohol consumption in men with low CSF 5-HIAA, who also exhibit impaired impulse control and violent and antisocial behaviors.