Changes in cortical and subcortical levels of monoamines and their metabolites following unilateral ventrolateral cortical lesions in the rat

Suction lesions were made in the anterior, posterior or both halves of the right ventrolateral cortex in rats. Six days later, levels of the monoamine neurotransmitters, norepinephrine (NE), dopamine (DA) and serotonin (5-HT), and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), were measured in cortical and subcortical regions of lesioned rats and compared to values in sham-operated animals. NE and 5-HT were decreased in sections of ipsilateral (right) cortex including, and posterior to lesions, while 5-HIAA was increased throughout the ipsilateral cortex. Decreases in monoamines and increases in metabolites and metabolite:monoamine ratios (especially 5-HIAA:5-HT) were found in ipsilateral subcortical structures, including striatum, nucleus accumbens, hippocampus, hypothalamus, midbrain and brainstem, depending on the type of lesion. Subacutely, focal ventrolateral cortical lesions may profoundly alter the levels and utilization rates of monoamine neurotransmitters in widespread regions of the ipsilateral hemisphere.     

Regional neurochemical studies on the effect of beta, beta'-iminodipropionitrile (IDPN) in the rat.

A permanent hyperkinetic syndrome, characterized by excitation, choreiform head and neck movements and circling, which has led to it being called collectively the "ECC-syndrome," is induced in rats by the daily IP administration of beta, beta'-iminodipropionitrile (IDPN), 300 mg/kg, for 7 days. The levels of the biogenic amines, norepinephrine (NE), dopamine (DA), serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), were measured in the striatum, midbrain, medulla, cortex, and cerebellum on the day the syndrome appeared (day 7) and one week later (day 14). The biogenic amine most affected by IDPN administration was 5-HT. On day 7, striatal 5-HT levels increased and 5-HIAA levels decreased while in the medulla and midbrain, 5-HIAA levels increased. On day 14, significant reductions in both 5-HT, in the midbrain, striatum, and cortex, and 5-HIAA, in all regions except the cortex, were observed. NE was markedly increased in the medulla, midbrain, and striatum on day 7, whereas on day 14 it was found to be within the normal range in these same regions. With the exception of a slight, but significant, increase in the cortex on day 7, DA levels in all regions were found to be relatively unaffected by IDPN administration on both day 7 and day 14. In an attempt to detect degenerative changes which might be taking place in the brain and which might provide an explanation for the permanency of the behavioral disturbances, the uptake of [3H]-labeled NE, DA, and 5-HT into synaptosomal-rich preparations of striatum and the uptake of NE and 5-HT into the midbrain area were compared between normal and syndromized rats on both day 7 and day 14. Small changes were observed but they were not statistically significant. The alterations of 5-HT and 5-HIAA levels in several regions of the brain under the conditions examined may indicate that IDPN's neurotoxicity primarily affects 5-HT-containing neurones. The active membrane transporting system of the nerve endings studied, however, remained relatively intact. This latter finding eliminates the possibility that neuronal degeneration in these areas is responsible for the decreased 5-HT and 5-HIAA levels or is the pathology underlying the permanency of the syndrome. These results are evaluated in terms of a possible model for hyperkinetic disorders.     

Dorsal lesions of the prefrontal cortex: effects on alcohol consumption and subcortical monoaminergic systems

Male Wistar rats were subjected to either bilateral aspiration lesions of the dorsal regions of the prefrontal cortex (PFC) or sham lesions and placed on a 6-week, modified sucrose-fading procedure. At the time of sacrifice, the size of the lesion, both in anterior-posterior and medial-lateral dimensions, was measured. Following sacrifice, levels of dopamine (DA), serotonin (5-HT), norepinephrine (NE), and their metabolites were measured in the midbrain (raphe) and nucleus accumbens (NA). Lesioned animals had reductions in 5-HT in the NA, and DA and NE in the raphe. The lesioned group drank more of a solution of 5% alcohol than controls early in the sucrose fading, and less during the later stages. In the lesioned group, the size of the left- and right-hemisphere lesions predicted 5-HIAA levels in the NA, and 5-HT and 5-HIAA levels in the raphe. A laterality effect was noted, such that the size of left-hemisphere lesions were positively associated with raphe 5-HT and 5-HIAA levels, and negatively associated with 5-HT levels in the NA, while right-hemisphere lesions showed the opposite relationships. In addition, the width of the left-hemisphere lesion predicted some measures of alcohol intake. These results suggest that, in the rat, the dorsal PFC is involved in the regulation of monoamines in subcortical regions known to be important in the regulation of reinforced behaviors, and that this regulation differs between hemispheres and shows a laterality effect. In addition, the dorsal PFC appears to have a subtle involvement in the regulation of alcohol intake.     

Effects of neonatal rat Borna disease virus (BDV) infection on the postnatal development of the brain monoaminergic systems

Effects of neonatal Borna disease virus infection (BDV) on the postnatal development of brain monoaminergic systems in rats were studied. Tissue content of norepinephrine (NE), dopamine (DA) and its metabolite, 3,4-dihydroxyphenol acetic acid (DOPAC), and serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) were assayed by means of HPLC-EC in frontal cortex, cerebellum, hippocampus, hypothalamus and striatum of neonatally BDV-infected and sham-inoculated male Lewis rats of 8, 14, 21, 60 and 90 days of age. Both NE and 5-HT concentrations were significantly affected by neonatal BDV infection. The cortical and cerebellar levels of NE and 5-HT were significantly greater in BDV-infected rats than control animals at postnatal days (PND) 60 and 90. Tissue content of NE in hippocampus was unaffected. In hippocampus, neonatally BDV-infected rats had lower 5-HT levels at PND 8 and significantly elevated levels at PND 21 and onwards. Neither striatal levels of 5-HT nor hypothalamic levels of 5-HT and NE were affected by neonatal BDV infection, suggesting that the monoamine systems in the prenatally maturing brain regions are less sensitive to effects of neonatal viral infection. 5-HIAA/5-HT ratio was not altered in BDV-infected rats indicating no changes in the 5-HT turnover in the brain regions damaged by the virus. Neither DA nor DOPAC/DA ratio was affected by neonatal BDV infection in any of the brain regions examined. The present data demonstrate significant and specific alterations in monoaminergic systems in neonatally BDV-infected rats. This pattern of changes is consistent with the previously reported behavioral abnormalities resulting from neonatal BDV infection.     

Variations of monoamines and their metabolites in the human brain putamen

The levels of the monoamines dopamine (DA), serotonin (5-HT) and norepinephrine (NE) and the monoaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured with HPLC-ECD in 42 samples from human brain putamen. The influence of gender and of age was investigated and correlations between the monoamines were established. The DAergic system shows a significant difference between males and females, with females having lower DA and higher DOPAC levels and a higher DOPAC/DA ratio than males. No gender-related differences of 5-HT and its metabolites were observed, nor of NE. Three different age groups (group 1: 0–9.9 years; group 2: 10–59.9 years; group 3: 60 years and older) were defined according to previous studies on ontogenesis and senescence in human brain. An increase in 5-HT levels, decrease in 5-HIAA levels a d a decrease in the 5-HIAA/5-HT ratio were observed after the first decade of life. Changes in the DAergic system were seen in senescence, with decreasing DA levels and an increase in the HVA/DA ratio. DOPAC, HVA and the DOPAC/DA ratio are unaffected. NE is similar in all age groups. The analysis of the relation of the levels of the three monoamines proved a strong correlation between the DAergic and 5-HTergic systems. The nature of this relationship might have an impact on neuro-psychiatric disorders and brain function.     

Recovery from lateralized neocortical damage: dissociation between amphetamine-induced asymmetry in behavior and striatal dopamine neurotransmission in vivo

It has been hypothesized that neocortical damage is accompanied by secondary changes in other brain areas (the shock or diaschisis of von Monakow), which contributes to initial non-specific behavioral depression. The relation between behavioral changes and dopamine (DA), serotonin (5-HT), and their metabolites, measured with intracerebral microdialysis in freely moving rats and by tissue assay postmortem, was examined during postsurgical recovery from unilateral hemidecortications. Rats were tested for rotational asymmetry and extracellular concentration of DA was measured both during rest and after amphetamine (1.5 mg/kg). It was found that: (1) during the first few postsurgical days the hemidecorticate rats rotated ipsilateral to their lesions after amphetamine but thereafter on tests given up to 121 days postsurgery there was no asymmetry in rotation; (2) there were no asymmetries in the concentration of DA or its metabolites at any time after surgery; (3) the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) was elevated acutely for a few days following surgery; (4) during the first 3 postoperative days, both baseline extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) and amphetamine-induced DA release were significantly elevated bilaterally. These findings demonstrate that the acute behavioral asymmetry in rotation produced by hemidecortication is not related to unilateral changes in striatal DA activity and its metabolites. Thus, the behavioral asymmetries might be related to other striatal changes (i.e. 5-HIAA) or other damage, such as to the corticospinal projections of the lesioned hemisphere. Nevertheless, unilateral lesions did produce acute bilateral increases in DA levels, which may be a correlate of generalized neural shock produced by the lesion.     

Monoamines and metabolites in cortex and subcortical structures: normal regional distribution and the effects of thiamine deficiency in the rat

The present study measured the concentration of monoamines, metabolites and estimates of turnover rate in eighteen separate brain regions from controls and a rat model of Korsakoff's disease induced by a two week bout of pyrithiamine and thiamine deficient diet (PTD). A behaviorally tested control (n = 12) and PTD (n = 17) group, and a non-behaviorally tested PTD group (n = 8) were sacrificed 7 months after recovery from treatment. The brains were dissected into nine cortical areas and nine subcortical regions. In behaviorally tested PTD animals, a significant reduction of NE was observed in entorhinal cortex. Diminished norepinephrine (NE) concentration was also observed in entorhinal, hippocampal, septal and olfactory areas of the non-behaviorally tested PTD group. Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels were increased in several brain areas, particularly midbrain-thalamus, striatum, of both groups of recovered PTD animals. These findings are discussed with respect to results and hypotheses presented in our previous study of this animal model. Significant differences in monoamine, metabolite and turnover estimates were also observed among cortical areas of the control animals. Entorhinal cortex contained the highest concentration of NE and 5-hydroxytryptamine (5-HT), while DA was highest in somatosensory cortex. The distribution of 5-HT and 5-HIAA were more homogeneous and displayed a rostral-caudal decline in concentration.     

Simultaneous HPLC quantification of monoamines and metabolites in the blood-free rat cochlea

Monoamine quantification in peripheral sensory receptors, such as the cochlea, is of major interest since monoamines could play a role in neurotransmission. A three-step biochemical protocol was developed to analyze monoamine content within the cochlea. Removal of the blood by aortic perfusion was carried out with an anticoagulant solution prior to the dissection of the cochlea from the temporal bone. The cochlear monoamines and some of their metabolites were then quantified, from homogenated cochlear tissue, by a new application of high performance liquid chromatography coupled to electrochemical detection. This method demonstrated enough sensitivity to detect norepinephrine (NE), dopamine (DA), serotonin (5-HT) and some of their metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; homovanillic acid, HVA; and 5-hydroxyindole-3-acetic acid, 5-HIAA). Furthermore, it enabled the demonstration of noise-induced changes in the cochlear concentrations of NE, DA, DOPAC and HVA. In addition, the aortic perfusion allowed removal of the blood-borne 5-HT from the cochlea without inducing systemic alterations or monoamine degradation, as shown by the absence of effects on NE, DA, DOPAC, HVA or 5-HIAA concentrations. The present methodology may constitute a useful strategy to analyze monoamine turnover in the cochlea and other peripheral sensory receptors.     

Analysis of temporal and dose-dependent effects of estrogen on monoamines in brain nuclei

Levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were measured in hypothalamic and limbic nuclei of ovariectomized rats after various doses of estradiol and at various intervals after estradiol administration. Of 13 areas examined, time- and dose-dependent effects of estrogen on monoamine content were restricted to only a few, discrete areas which concentrate estradiol. Subcutaneous administration of 1-50 micrograms of estradiol benzoate (EB) and measurement of monoamines 24 h later was associated with dose-dependent increases of NE in the medial preoptic nucleus, diagonal band nucleus and periventricular area of the anterior hypothalamus, and increased levels of DA in the periventricular area of the preoptic area. No changes were found in 5-HT levels, but dose-dependent increases in the level of the 5-HT metabolite, 5-hydroxyindole acetic acid (5-HIAA), were measured in the lateral portion of the ventromedial nucleus. Effects of 5 micrograms of EB were evaluated at 1.5, 6, 12 and 45 h after administration. No changes were noted at 1.5 h, but 5-HIAA in the ventromedial nucleus was elevated at 6 and 12 h. NE levels were elevated at 12 and 45 h in the diagonal band and preoptic nuclei and at 45 h in the lateral septum and periventricular area of the hypothalamus. DA levels decreased in the arcuate-median eminence area 45 h after estrogen. Intravenous administration of 10 micrograms of estrogen and measurement of monoamines 1 h later was not associated with altered levels of any monoamine suggesting that the estrogen-dependent changes are consistent with the genomic model for steroid hormone action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naltrexone administration effects on regional brain monoamines in developing rats

The effects of the opioid antagonist naltrexone (NALTX) daily administration (1 mg/kg SC) from birth on the levels of dopamine (DA), serotonin (5-HT), and their respective major metabolites, in the striatum, midbrain, and hypothalamus of 7-, 14-, and 22-day-old rats were investigated. Naltrexone treatment increased the striatal HVA/DA ratio on postnatal day 7. At day 14, two subpopulations (A and B) were found among the treated animals. The subpopulation A showed decreased HVA/DA and increased DOP AC/DA ratios, whereas the subpopulation B presented a higher DA concentration. No significant effect appeared on the striatal dopaminergic system in 22-day-old pups. The serotonergic system was affected by exposure to naltrexone only from day 14. The subpopulation A showed a reduction in all the parameters measured in the three regions studied, although in the subpopulation B, lower 5-HIAA/5-HT ratios appeared in the midbrain and hypothalamus. At 22 days of age NALTX treatment elevated striatal 5-HT and 5-HIAA and the ratio of 5-HIAA/ 5-HT in the midbrain and hypothalamus. These data suggest an endogenous opioid modulation on the central aminergic systems during the neonatal period and point out the consequences of opioid plasticity on related neurotransmitter systems.     

Topographical dopamine and serotonin distribution and turnover in rat striatum

Topographic distribution of dopamine (DA), serotonin (5-HT), dihydroxyphenylacetic acid (DOPAC), hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) was determined in rat striatum using high-pressure liquid chromatography (HPLC) with electrochemical detection. The ratios of DOPAC:DA and 5-HIAA:5-HT were calculated as indices of turnover of DA and 5-HT. There was a rostro-caudal gradient for both DA and 5-HT, with DA highest in rostral striatum and 5-HT highest in caudal striatum (P less than 0.01). DA concentrations in the coronal plane showed a homogeneous distribution except at the level of the globus pallidus. DOPAC also showed a rostro-caudal gradient and concentrations were significantly increased in the nucleus accumbens (P less than 0.01). DOPAC:DA ratios were significantly increased in both the nucleus accumbens and the ventromedial striatum as compared to the remaining striatal punches. 5-HT was more heterogeneously distributed in the coronal plane with concentrations highest in the ventromedial and the ventrolateral quadrants, where they were 2-3-fold higher than in dorsal striatum (P less than 0.01). Concentrations of 5-HIAA were highest in the nucleus accumbens and ventromedial striatum but HIAA-5-HT ratios were highest in the dorsolateral striatum (P less than 0.01). DA turnover is therefore highest in limbic innervated (n. accumbens and ventromedial) striatum while 5-HT turnover is highest in sensorimotor innervated (dorsolateral) striatum. These findings provide further evidence for functional compartmentalization within the striatum.     

Effects of valproate on amino acid and monoamine concentrations in striatum of audiogenic seizure-prone balb/c mice

The effects of aalproate on CNS concentrations of γ-aminobutyric acid (GABA), glutamate (GLU), glutamine (GLN), dopamine (DA), serotonin (5-HT), and metabolites were examined in tissue extracts of caudate nucleus of genetic substrains of Balb/c mice susceptible (EP) or resistant (ER) to audiogenic seizures. Generalized tonic-clonic seizures observed in EP mice were inhibited by valproate, administered 1 h prior to testing, in a dose-response fashion. Concentrations of GABA, GLU, and GLN, which were lower in EP mice than in ER mice, were significantly increased by valproate at doses of 180 and 360 mg/kg. Concentrations of homovanillic acid (HVA) and hydroxyindoleacetic acid (5-HIAA), metabolites of DA and 5-HT were substantially increased by valproate at these doses. Thein situ activity of tyrosine hydroxylase (TH) was not significantly influenced by valproate, whereas a valproate-induced increase in tryptophan hydroxylase (TPH) activity was observed in both striatum and in midbrain tegmentum. The data are consistent with the interpretation that anticonvulsive doses of valproate influences the intraneuronal metabolism of monoamines, GABA, and glutamate concurrently. Valproate’s influence on the metabolism of both major inhibitory (GABA) and excitatory (GLU) amino acids in striatum could contribute to its anticonvulsive effects in genetically seizure-prone mice, as well as to the accumulation of DA and 5-HT metabolites.     

Effects of ketamine on dopamine metabolism during anesthesia in discrete brain regions in mice: comparison with the effects during the recovery and subanesthetic phases

The effects of ketamine on the levels of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT, serotonin) and their metabolites were examined in discrete brain regions in mice. A high dose of ketamine (150 mg/kg, i.p.) did not change DA metabolism in the frontal cortex, nucleus accumbens, striatum and hippocampus, but did decrease it in the brainstem during anesthesia. In contrast, during recovery from the ketamine anesthesia, the high dose increased the level of homovanillic acid (HVA) in all brain regions. A low subanesthetic dose of ketamine (30 mg/kg, i.p.) increased the concentrations of both 3,4-dihydroxyphenylacetic acid (DOPAC) and HVA only in the nucleus accumbens. The DA level was not affected by any ketamine treatment. During ketamine anesthesia, the content of 3-methoxy-4-hydroxy-phenylglycol (MHPG) was decreased in the brainstem, whereas during recovery from anesthesia, the MHPG level was increased in the frontal cortex, nucleus accumbens and brainstem. The NE content was not altered in any region by ketamine treatment. The concentration of 5-hydroxyindoleacetic acid (5-HIAA) was reduced in the frontal cortex, striatum, hippocampus and brainstem during ketamine anesthesia. The 5-HT level was unaltered in all regions except the brainstem where it was reduced. In contrast, after anesthesia, the concentrations of both 5-HT and 5-HIAA were increased in the striatum. During the subanesthetic phase, however, the levels of NE, 5-HT and their metabolites were unchanged. These neurochemical results are consistent with the electrophysiological findings that a high dose of ketamine does not change the basal firing rates of nigrostriatal DA neurons during anesthesia, while low subanesthetic doses significantly increase those of ventral tegmental DA neurons.     

Effect of chronic nicotine administration on monoamine and monoamine metabolite concentrations in rat brain

The effects on rat brain tissue monoamine and monoamine metabolite concentrations of chronic nicotine administration at two doses (3 and 12 mg/kg/day) using constant infusion were studied. After 21 days of treatment, tissue concentrations of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and several metabolites in striatum, hypothalamus, and frontal cortex were determined by high performance liquid chromatography with electrochemical detection. Compared with a control group, nicotine treatment significantly decreased NE in frontal cortex but not in other regions. The concentration of 5HT also was decreased in frontal cortex but increased in the hypothalamus at the higher dose of nicotine. The 5HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) was not significantly altered in any region. The 5HT index (5-HIAA/5-HT) was significantly decreased in the hypothalamus and increased in frontal cortex at the higher dose. Concentrations of DA and the metabolite homovanillic acid (HVA) were not significantly altered by nicotine. Nevertheless, significant decreases in the DA metabolite dihydroxyphenyl-acetic acid (DOPAC) were observed in both striatum and hypothalamus. Moreover, the DA index [(DOPAC + HVA)/DA] was significantly decreased in all three brain regions. In contrast to other studies using acute dose and in vitro perfusion paradigms that have reported increased CNS catecholamine release stimulated by nicotine, chronic administration appears to be associated with decreased catecholamine turnover in some brain regions.     

Modification of gonadectomy-induced increases in brain monoamine metabolism by steroid hormones in male and female rats

Concentrations of monoamines (dopamine, DA; serotonin, 5-HT) and their major metabolites (homovanillic acid — HVA; dihydroxyphenylacetic acid — DOPAC; 5-hydroxyindolacetic acid — 5-HIAA) were measured in selected brain areas of chronically gonadectomized, steroid- or oil-treated male and female rats. Concentrations of DOPAC and HVA were markedly increased in the hypothalamus (male, female), striatum (male, female) and brainstem (male) following gonadectomy, whereas the levels of DA remained unaltered in most of the brain areas examined. Most of the changes were reversed or attenuated by chronic estradiol (EB) substitution. In contrast, chronic treatment with physiological concentrations of testosterone (TP) reduced indexes of DA turnover only in the striatum of ovariectomized (OVX) and brainstem of orchidectomized (ORDX) rats. ORDX-related increases in striatal levels of DOPAC and HVA were not reversed by either EB or TP. ORDX increased the levels of 5-HIAA (hypothalamus, striatum) and decreased those of 5-HT (hypothalamus, hippocampus). These changes were reversed by chronic treatment with either TP or EB. Brain metabolism of 5-HT remained unaltered following OVX.

Gonadectomy and chronic steroid replacement therapy appear to alter brain monoamine metabolism in a brain region and sex-dependent manner. Our data demonstrate that gonadectomy-related increases in the activity of brain monoaminergic neurons in both male and female rats was attenuated more effectively with physiological concentrations of estradiol than with testosterone. Insensitivity of monoaminergic neurons in a number of brain areas (e.g., hypothalamus, striatum) to the action of testosterone was evident in both sexes.     

Estradiol modulation of central monoamine activity in female mountain spiny lizards

Although estradiol (E2) mediates many behaviors in females, relatively little is known about its role in female aggression. Previous studies in female mountain spiny lizards indicated that female aggression is modulated by ovariectomy and sex steroid hormone replacement and that expression of aggressive behavior is accompanied by changes in serotonin activity. This study examines if E2 modulates the activity of serotonin and other central monoamines. Free-living females were caught and housed in the laboratory and received one of 3 treatments: sham surgery (SHAM), ovariectomy plus empty implant (OVEX), or sham surgery plus a long lasting E2 implant (E2-IMP). After 3 weeks of treatment, selected brain areas were examined for levels of monoamines and their metabolites. Changes in monoamine activity were most pronounced in the septum where levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine (NE) were higher in E2-IMP females relative to SHAM, and levels of 5-HIAA were higher in OVEX females relative to SHAM. Changes in dopamine (DA) activity were also found, with increased DA concentration and decreased ratio of forebrain:brainstem HVA concentrations in E2-IMP relative to SHAM females. These results suggest that the actions of E2 on aggression might be mediated, in part, by dose-dependent effects on 5-HT activity in the septum.     

Spinal cord monoaminergic system response to age and cold-acclimatization in Muscovy duckling

Summary. The effect of age and cold acclimatization on the regional distribution of monoamines in duckling spinal cord was studied. In thermoneutral controls (TN), the high dopamine (DA) to norepinephrine (NE) ratios (0.25 at 4 weeks of age and 0.15 at 6 weeks of age) suggest the presence of specific (non precursor) dopaminergic pools in cervical spinal cord. DA levels and the ratio of DA to NE were lowered by age and cold exposure in the cervical cord. In TN ducklings, serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) showed a decline with age in the spinal cord, indicating that this system is affected with development, whereas cold exposure prevents this decrease. The contents of 5-HT (+58%), 5-HIAA (+93%) and the ratio of 5-HIAA to 5-HT (+50%) are higher in the cervical spinal cord of cold acclimated than in TN ducklings. These results indicate that central monoaminergic systems are markedly affected by age and cold exposure. Received November 11, 1999; accepted March 6, 2000     

Bilateral augmentation of dopaminergic and serotonergic activity in the striatum and nucleus accumbens induced by conditioned circling

The involvement of dopaminergic (DA) and serotonergic (5-HT) systems in circling was assessed by determining the neurochemical correlates of circling induced and maintained by two different schedules of water reinforcement. The conditioned circling paradigm was employed in an attempt to replicate reports that levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) were increased in the striatum and nucleus accumbens septi (NAS) contralateral to the direction of circling. Rats trained to circle using a continuous schedule of reinforcement did not exhibit any changes in concentrations of DA, DOPAC, or homovanillic acid (HVA). Bilateral increases in 5-HT concentrations were observed in the striatum. Use of an intermittent schedule of reinforcement (FR-2) produced higher rates of circling. In rats maintained on the FR-2 schedule, no changes in DA or its metabolites were observed in the striatum. The ratio of HVA to DA was, however, increased bilaterally, suggesting a bilateral augmentation of DA utilization. Concentrations of DA were lower in the NAS contralateral to direction of turning. While NAS levels of HVA were elevated bilaterally when compared to non-circling controls, HVA was lower in the NAS contralateral to the direction of circling. DA utilization, as estimated by HVA: DA ratios, was increased bilaterally in the NAS. None of the measures of DA activity within the olfactory tubercle (OT) were influenced by circling. Turnover of 5-HT, as estimated by the ratio of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA), was increased bilaterally in the striatum, NAS, and OT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spatial memory deficits in aged rats: contributions of monoaminergic systems

Age-dependent changes in monoaminergic systems and their relationship to senescent memory decline were investigated in 4- and 25-26-month-old, female, Fischer 344 rats. Spatial memory performance was tested on an 8-arm radial maze, and levels of norepinephrine (NE), dopamine (DA) and metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, serotonin (5-HT) and metabolite 5-hydroxyindoleacetic acid were measured in brain areas which contribute to memory function--basal forebrain cholinergic nuclei, subfields of the hippocampus, frontal and entorhinal cortex--and in monoaminergic cell body areas. The performance of aged subjects was significantly impaired as compared to young subjects, and alterations of 20-60% in monoamine and metabolite levels were measured in specific brain areas of aged rats. Decreased NE levels were found in basal forebrain nuclei and cortical areas but not in hippocampal subfields of aged rats. Changes in the 5-HT system were present in hippocampal, cortical and basal forebrain sites. Changes in the DA system were the most pervasive with aged rats showing decreased DA and/or metabolites in several basal forebrain nuclei, cortical areas, and the hippocampus. Aged rats showed 50% decreases of monoamines in locus coeruleus and substantia nigra and 30% decreases in the dorsal raphe nucleus. Some but not all of the changes correlated with memory performance. The present results in rats support evidence that age-dependent changes in monoaminergic function in discrete brain sites contribute to senescent memory decline and suggest that monoaminergic-cholinergic interactions within basal forebrain nuclei may be important in this decline.     

Pineal melatonin and brain transmitter monoamines in CBA mice during chronic oral nicotine administration

The effects of chronic oral nicotine administration on the pineal melatonin and brain transmitter monoamines were studied in male CBA mice, which possess a clear daily rhythm of melatonin secretion. On the 50th day of nicotine administration, pineal melatonin as well as cerebral dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined at various times. The chronic nicotine treatment did not alter the timing of the pineal melatonin peak, which occurred at 10 h after the light offset. However, in mice drinking nicotine solution, the nocturnal pineal melatonin levels were lower than in control mice drinking tap water. The chronic nicotine treatment increased the striatal DA, DOPAC, HVA and 5-HIAA levels, the hypothalamic NE, MHPG and 5-HIAA and the cortical MHPG. Most prominent effects of nicotine were found at 8 h after the light offset, when the striatal levels of DA and HVA, hypothalamic NE and MHPG as well as cortical MHPG were significantly elevated in the nicotine-treated mice compared with the control mice. No direct correlation between nicotine's effects on brain transmitter monoamines and on pineal melatonin levels was apparent. The results suggest that chronic nicotine treatment slightly suppresses the melatonin production but does not alter the daily rhythm of pineal melatonin in mice maintained on a light-dark cycle. However, the results indicate that nicotinic receptors might be involved in the regulation of pineal function.