Laparoscopic vs conventional appendectomy--a meta-analysis of randomised controlled trials

A comparison was made of the dynamics of sympathoadrenal activity in 11 age-matched male and female rats, under basal conditions and after exposure to footshock. Rats were prepared with indwelling catheters in the tail artery 24 h before the experiment. Measurements were made of plasma corticosterone (COR), norepinephrine (NE), epinephrine (EPI), dihydroxyphenylalanine (DOPA), dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) under resting conditions, after transfer to the shock box (novelty) and at various times after footshock. Under basal conditions, males have significantly higher blood pressure and plasma DHPG/NE ratios but lower plasma levels of COR, NE and DOPAC than females. Three min after exposure to the shock chamber (novelty stress) there were significant increases in COR, EPI, NE and DHPG in both sexes, while DOPA increased only in females and DOPAC remained unchanged in both sexes. Footshock produced a further increase in EPI, NE and DOPAC within 2 min, which lasted about 15 min. There were significant sex differences in the extent and duration of the response of COR, EPI and DHPG. The data show that the female sympathoadrenal system is more reactive than that of the male to the stresses of a novel environment and footshock. The smaller DHPG/NE ratios in females at rest and after stress suggest that neuronal uptake of NE is lower in females than in males. The finding that stress produces larger increments of plasma DOPA and DOPAC in female rats indicates that tyrosine hydroxylase in the sympathetic nerve terminals and adrenal medulla may also be higher than in males.     

Changes in brain catecholamine metabolism during bromocriptine treatment in polycystic ovary syndrome

The role of dopaminomimetic drugs on the brain catecholamine metabolism in the neuroendocrine regulation of the polycystic ovary syndrome (PCO) was investigated. We measured, besides peptide hormones and sex steroids, urinary dopamine (DA), norepinephrine, epinephrine, vanillylmandelic acid, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and total 3-methoxy-4-hydroxyphenylglycol (MHPG) levels by high-performance liquid chromatography with electrochemical detector in 10 women with PCO before and during long-term bromocriptine (BRC) administration. HVA and DOPAC concentrations were significantly lower (p < 0.001) in PCO patients compared with 12 control subjects in the early follicular phase, whereas MHPG concentrations were significantly higher (p < 0.01) in PCO patients. During BRC administration, HVA, DOPAC and MHPG levels increased significantly (p < 0.01 for HVA and DOPAC, and p < 0.05) for MHPG), prolactin levels dropped markedly (p < 0.01), whereas luteinizing hormone levels did not change (p = NS). These data show (1) a reduced DA activity in PCO which may be normalizable under BRC treatment, but also (2) no major effects of DA metabolism on the inappropriate gonadotropin secretion of the syndrome.     

Blocking effects of ethanol on stress-induced activation of rat mesoprefrontal dopamine neurons

We investigated the effects of ethanol on stress-induced activation of the brain dopamine (DA) systems in rats. Ethanol (0.5 and 1.0 g/kg) was injected IP 25 min before sacrifice (5 min before 20-min immobilization stress). Ethanol treatment by itself did not affect the levels of either DA or its major metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the mesoprefrontal cortex, cingulate cortex, olfactory tubercle, or caudate putamen. Immobilization stress for 20 min caused increases in DOPAC levels in the prefrontal cortex (160% of control) and cingulate cortex (135% of control), but not in the olfactory tubercle or caudate putamen. The stress had no effects on DA levels in any of the four brain regions studied. Pretreatment with ethanol blocked, in a dose-dependent manner, the stress-induced increases in DOPAC levels in the mesoprefrontal cortex. The present data suggest that ethanol exhibits a blocking effect on stress-induced activation of the mesoprefrontal DA neurons. This blocking effect may be related to the anxiolytic action of ethanol.     

Effect of anoxia on striatal monoamine metabolism in immature rat brain compared with that of hypoxia: an in vivo microdialysis study

We examined in 5-day-old rats the effects of either anoxia or 8% hypoxia on extracellular monoamines such as dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole-3-acetic acid (5-HIAA) using in vivo microdialysis and subsequent HPLC. After stabilization 64 animals were exposed to 100% nitrogen for 16 min and 40 animals to 8% oxygen for 128 min. Both anoxia and hypoxia produced acute increase in the striatal extracellular DA (anoxia: P < 0.001, hypoxia: P < 0.01). Especially in anoxia, DA levels increased transiently to 2000-times the basal levels and 6-times higher than those in hypoxia. NE also increased in both anoxia and hypoxia. DOPAC and HVA decreased during hypoxia (P < 0.01 and P < 0.001, respectively), while those in anoxia were unchanged. In anoxia, decrease tendency of their levels were in short duration and that of 5-HIAA was followed by gradual increase (P < 0.001). These data demonstrated that brief exposure to anoxia or hypoxia had significant influence on striatal monoamine metabolism in immature brain and the pattern of change of monoamine in anoxia was different from that in hypoxia.     

Parathyroid hormone-induced dopamine turnover in the rat medial basal hypothalamus

The parathyroid hormone (PTH) gene is expressed and translated in the rat hypothalamus, and the possibility that PTH may modulate neural activity was therefore examined in anesthetized rats. Intracerebroventricular (ICV) injections of 1.0 or 10.0 micrograms rat, human, or bovine PTH(1-34) was followed 60 min later by increased concentrations of DOPAC (dihydroxyacetic acid) and the DOPAC:dopamine (DA) ratio in the medial basal hypothalamus (MBH), but not in other (brainstem, cerebral cortex, cerebellum) regions of the brain. Tissue concentrations of norepinephrine and serotonin were unchanged by ICV PTH administration, although MBH concentrations of 5-hydroxyindolacetic acid (5-HIAA) were increased following PTH administration. An increase in MBH DA turnover (as indicated by an increased DOPAC:DA ratio) was also induced by the ICV injection of 10 micrograms PTH-related protein [PTHrP(1-34)]. Pretreatment with the receptor antagonists PTH(7-34) or PTHrP(7-34) completely blocked the subsequent DOPAC response to ICV PTH or PTHrP, respectively. The DOPAC concentrations in hypothalamic extracellular fluid (ECF), sampled by microdialysis, were also increased within 20 min of PTH(1-34) perfusion, in the absence of changes in the ECF concentrations of 5-HIAA. These results demonstrate that PTH and PTH-like peptides specifically increase DA turnover in the rat MBH and suggest novel roles for these hormones in neural regulation.     

Acute effect of 17 beta-estradiol and lithium on ovariectomized rat brain biogenic amines metabolism

The effect of 17 beta-estradiol (E2) on the response of dopamine (DA) and serotonin (5-HT) to acute lithium in the brains of ovariectomized rats was investigated. An E2 injection (100 ng/s.c.) to ovariectomized rats did not change striatal DA levels, whereas the levels of its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), increased 30 min later; concentrations of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), also remained unchanged. In the frontal cortex, DA, 5-HT, HVA and 5-HIAA levels remained unchanged after the E2 injection, whereas DOPAC levels and DOPAC/DA and HVA/DA ratios increased 30 min later. Injection of LiCl (10 mEq) decreased striatal DA levels, increased DOPAC levels and slightly decreased HVA levels; by contrast, frontal cortex DA and HVA levels increased but DOPAC levels were unchanged. A biphasic response of striatal 5-HT levels occurred, increasing shortly after injection of LiCl, followed by a decrease; 5-HIAA levels, however, increased. In the frontal cortex, injection of rats with LiCl led to a gradual increase in 5-HT levels, whereas 5-HIAA concentrations decreased. In the presence of E2, LiCl effected a greater decrease in striatal DA than injection of LiCl alone, advanced the DOPAC peak by 30 min and increased HVA levels; E2 had less effect on the 5-HT response to LiCl, except the decreases in 5-HT and 5-HIAA at 60 min were greater. Furthermore, in the striatum, the increased DA turnover caused by LiCl, estimated by the DOPAC/DA and HVA/DA ratios, was advanced in rats treated with E2. In the presence of E2, LiCl slightly increased frontal cortex DA, DOPAC and HVA levels compared with treatment with LiCl alone, whereas DOPAC levels decreased in rats treated with LiCl + E2 compared with levels in E2-treated rats. Generally, higher levels of 5-HT and 5-HIAA were measured in the frontal cortices of rats treated with LiCl + Ex compared with rats injected with LiCl. These results indicate that E2 potentiates the acute effect of lithium on striatal and frontal cortex DA and 5-HT levels and metabolism, suggesting a role of the hormonal state on this drug response.     

Effects of lead-arsenic combined exposure on central monoaminergic systems

Lead acetate (116 mg/kg/day), arsenic (11 or 13.8 mg/kg/day as sodium arsenite), a lead-arsenic mixture or vehicle were administered to adult mice through gastric intubation during 14 days. Then, the regional content of norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4 dihydroxyphenyl-acetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HIAA), arsenic, and lead were quantified. Compared with the accumulation after single element exposures, the mixture elicited a higher accumulation of lead and a lower arsenic accumulation in the brain. Compared to controls, lead induced only an augmentation of DOPAC (200%) in the hypothalamus. By contrast, the mixture provoked increases of DOPAC in the hypothalamus (250%), DA and 5-HIAA in the striatum (67 and 187%, respectively) and NE decreased in the hypothalamus (45%). Although these alterations were similar to those produced by arsenic alone, the mixture provoked a 38% decrease of NE in the hippocampus and increases of 5-HT in midbrain and frontal cortex (100 and 90%, respectively) over control values, alterations that were not elicited by either metal alone. These results demonstrate an interaction arsenic/lead on the central monoaminergic systems of the adult mouse.     

Effect of morphine applied by intrapallidal microdialysis on the release of dopamine in the nucleus accumbens

The effect of morphine, administered intrapallidally, on extracellular concentrations of DA, DOPAC, and HVA in the nucleus accumbens and striatum was studied in the behaving rat using the in vivo microdialysis technique. Unilateral application of morphine hydrochloride was performed through microdialysis probes into the rat ventral pallidum (10 microliters of 0, 2.6, 4.0, 13.0, and 26.0 mM) or globus pallidus (10 microliters of 0 and 26.0 mM). The levels of DA, DOPAC, and HVA were measured using the HPLC with EC detection in dialysates collected from the nucleus accumbens, anteromedial, and anterolateral striatum. Samples were taken every 45 min over 3 h before and over 5 h after morphine or vehicle administration. Administration of morphine into the ventral pallidum resulted in increased DOPAC and HVA concentrations in the nucleus accumbens. Pretreatment with naloxone (1 mg/kg, SC) abolished this effect of morphine. Administration of morphine into the globus pallidus resulted in increased DA, DOPAC, and HVA concentrations in the nucleus accumbens and DA in the anteromedial striatum. The levels of DA and metabolites in anterolateral striatum remained rather unchanged following morphine administered into the ventral pallidum or the globus pallidus. The changes in DA neurotransmission into the nucleus accumbens induced by morphine application into the ventral pallidum and globus pallidus are reminiscent of a phasic and tonic release of DA respectively. The results show that intrapallidal morphine increases DA neurotransmission in nucleus accumbens and suggest that the effect of morphine is mediated by ventral pallidum/mesolimbic and globus pallidus/thalamocortical pathways, depending on the site of injection.     

Immunological evidences for post-translational control of the parathyroid function by ionized calcium in dogs

Recently, it has been reported that major depression is accompanied by an increased sympathoadrenal system (SAS) activity. In order to study the psychopathological correlates of SAS activity in depression, the authors measured the 24 h urinary excretion of catecholamines (CA), i.e., noradrenaline (NE), adrenaline (E), dopamine (DA) and the NE/E metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in 80 unipolar depressed subjects. The excretion of these indices of SAS activity have been studied in relation to the depressive items of the Structured Clinical Interview for DSM-III (SCID) and the Hamilton Depression Rating Scale (HDRS). There were significant positive correlations between the SCID item sleep disorders and the HDRS item middle insomnia, on the one hand, and NE, E and DA excretion, on the other. The MHPG excretion in 24 h urine was significantly and negatively related to somatic anxiety and hypochondriasis. It is suggested that these intertwined relationships between increased CA turnover, sleep discontinuity and anxiety may reflect the occurrence of a hyperarousal state in some major depressives that may be regarded as a coping response to various putative noxious stimuli.     

Hexadecylphosphocholine and 2-modified 1,3-diacylglycerols as effectors of phospholipase D

The effects of mesulergine (100 and 200 microg/kg s.c.), SB 206553 (1 and 2.5 mg/kg i.p.), RP 62203 (2.5 and 4 mg/kg i.p.) and ritanserin (630 microg/kg i.p.) were studied on the extracellular concentration of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens of chloral hydrate-anesthetized rats, using intracerebral microdialysis. Mesulergine, a non selective serotonin2C/2B/2A (5-HT2C/2B/2A) receptor antagonist, significantly increased DA release, which reached a peak level (+ 20%) 60 min after drug injection and slowly returned back to baseline values. Mesulergine also caused a dose-dependent increase in DOPAC outflow. Pretreatment with mesulergine (200 microg/kg) did not change the inhibition of DA release induced by apomorphine (100 microg/kg), whereas it prevented the reduction of DOPAC outflow induced by apomorphine (100 microg/kg). Administration of SB 206553, a selective blocker of 5-HT2C/2B receptors, dose-dependently increased DA outflow. The dose of 2.5 mg/kg SB 206553 caused a linear increase of DA output which reached a peak (+75%) 40 min after injection, while 1 mg/kg induced a more gradual increase of DA release which peaked (+54%) 60 min after administration of the drug. Treatment with RP 62203, a selective 5-HT2A receptor antagonist, did not produce any significant effect on DA outflow. Administration of ritanserin, a mixed 5-HT2A/2C receptor antagonist, did not cause any significant change of DA and DOPAC outflow. Taken together, these data indicate that selective blockade of 5-HT2/2B receptor subtypes increases DA release in the rat nucleus accumbens.     

Modulation of dopamine release in the nucleus accumbens by 5-HT1B agonists: involvement of the hippocampo-accumbens pathway

Changes in extracellular levels of dopamine (DA), DA metabolites DOPAC and HVA, and the serotonin metabolite 5-HIAA, were measured by microdialysis in the rat nucleus accumbens (n. acc) after treatments with serotonin (5-HT)1A (8-OH-DPAT) or 5-HT1B (RU 24969 and S-CM-GTNH2) receptor agonists. Subcutaneous injections of RU 24969 (0.02-2 mg/kg) dose-dependently decreased 5-HIAA levels (0 to -38%), and also induced long-lasting increases in DA levels (0 to +37%) and DOPAC (+11% at the dose 0.5 mg/kg) in the shell of the n. acc, whereas 8-OH-DPAT (0.25 and 0.5 mg/kg) reduced 5-HIAA levels (-25%) and very slightly increased DOPAC at the lower dose (+4%), but had no effect on DA levels. Three weeks after interruption of the subicular efferent projections, the increase in DA levels previously observed after systemic injections of RU 24969 was abolished. Microinjections of RU 24969 (10 micrograms/microliter) or S-CM-GTNH2 (3 micrograms/microliter) into the ventral subicular area reproduced the effects of systemic injections of RU 24969 cn DA levels and increased DOPAC (+13%; +19%, respectively) and HVA levels (+23%; +24%), with no significant change in 5-HIAA. It is concluded that: (1) serotonin interacts with the mesolimbic dopaminergic system through 5-HT1B, but not 5-HT1A, receptors: and (2) serotonin interaction with the mesolimbic dopaminergic system involves postjunctional 5-HT1B heteroreceptors located in the ventral subicular area, which modulate the activity of glutamatergic hippocampo-accumbens pathways and only secondarily alter DA levels in the n. acc. The possible relevance of these results for schizophrenia is discussed.     

Nonedible material elicits chewing and reduces the plasma corticosterone response during novelty exposure in mice.

Mice placed into novel cages showed elevations of plasma levels of corticosterone. This response was of greater magnitude when the more novel of two cages was used. When mice had a piece of aluminum foil or cardboard available in the novel cages, they avidly chewed these substances. In the high novelty cage, the presence of either foil or cardboard reduced the magnitude of the plasma corticosterone response at 30 and 60 min. Mice exposed to novel cages for 30 min on each of 6 consecutive days showed a decline in chewing across days, although chewing still occurred during the last exposure. The plasma corticosterone response increased from the first to the sixth day of exposure, although the availability of foil in the high novelty cage reduced this response across days. The availability of a highly palatable food (peanut butter chips) evoked little chewing in the high novelty cage and had no effect on the plasma corticosterone response at 60 min. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction with pups enhances dopamine release in the ventral striatum of maternal rats: a microdialysis study

A growing body of evidence suggests that an interference with dopamine (DA) transmission disrupts maternal behavior in the rat. The present brain microdialysis study was therefore conducted to investigate whether infants can modulate ventral striatal DA release in mother rats. There was a significant rise in the extracellular concentrations DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the ventral striatum when mothers were reunited with their litters following separation overnight. Nursing was the predominant behavior during this phase of the experiment. More active behaviors were elicited by soiling pups with flowerpot earth, and this was accompanied by further increases in DA, DOPAC, HVA, and 5-HIAA. It is suggested that pup-induced stimulation of ventral striatal DA release facilitates parental responses such as pup retrieval.     

Evidence for synthesis and release of catecholamines by human amniotic epithelial cells

The present study investigated the presence, possible synthesis and release of catecholamines (CA) by human amniotic epithelial cells (HAEC) using HPLC with electrochemical detection. The presence of CA was indicated by the detection of norepinephrine (NE), dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in extracts of cultured HAEC. Incubation of HAE cells in medium supplemented with 1-tyrosine (CA precursor) and tetrahydrobiopterin (tyrosine hydroxylase cofactor) significantly increased the production of catecholamines, suggesting CA synthesis by HAEC. In contrast, pharmacological inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine (MPT) significantly reduced CA production, further confirming CA synthesis by HAEC. Catecholamines were also detected in the cell incubation media, demonstrating the ability of HAEC to spontaneously secrete CA. Moreover, incubation of cells with 50 mM K+ for 10 min increased the amount of CA released into the medium. Additionally, the detection of DOPAC, a primary metabolite of DA, in HAEC strongly indicates that these cells contain DA metabolizing enzymes. The present results suggest that HAEC synthesize and release CA. These cells may be a possible candidate for transplantation therapy of neurodegenerative diseases such as Parkinson's disease and also may serve as a model to study the aspects of catecholaminergic activity.     

In vivo characteristics and localisation of carotenoid pigments in psychrotrophic and mesophilic Micrococcus roseus using photoacoustic spectroscopy

The mesolimbic dopaminergic system (MDS) has been shown to be implicated in feeding behaviors. The present experiment was conducted to examine the effects of the sensory properties of food ingested on MDS activity. Microdialysis coupled to high-performance liquid chromatography with electrochemical detection was employed to measure the extracellular levels of dopamine (DA) and its main metabolites (DOPAC and HVA) in the nucleus accumbens of freely moving rats. During microdialysis sessions rats had access or not to powdered foods varying in palatability: short cakes as highly palatable (HP) food and regular chow as low palatable (LP) food. In the absence of food, there were no alterations in extracellular levels of DA, DOPAC, and HVA. During feeding, DA rose significantly with a greater rise for the HP than the LP food. Levels of DOPAC and HVA only reached significance with the HP food. The results indicate that the MDS is activated on ingestion of food, and suggest that MDS activity is related to the rewarding properties of foods.     

Naloxone-precipitated changes in biogenic amines and their metabolites in various brain regions of butorphanol-dependent rats

Influence of a naloxone (an opioid receptor antagonist) challenge (5 mg/kg, IP) on levels of biogenic amines and their metabolites in various brain regions of rats infused continuously with butorphanol (a mu/delta/kappa mixed opioid receptor agonist; 26 nmol/microliter/h) or morphine (a mu-opioid receptor agonist; 26 nmol/microliter/h) was investigated using high-performance liquid chromatography with electrochemical detection (HPLC-ED). Naloxone precipitated a withdrawal syndrome and decreased the levels of: dopamine (DA) in the cortex and striatum, 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum, homovanilic acid (HVA) in the striatum, limbic, midbrain, and pons/medulla regions in butorphanol-dependent rats. However, the levels of norepinephrine (NE), serotonin (5-hydroxytryptamine; 5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the regions studied were not affected by naloxone-precipitated withdrawal. In addition, naloxone increased the HVA/DA ratio in the cortex, while this ratio was reduced in the limbic, midbrain, and pons/medulla. The reduction of 5-HIAA/5-HT ratio was also detected in the limbic area. In the animals rendered dependent on morphine, the results obtained were similar to those of butorphanol-dependent rats except for changes of 5-HIAA levels in some brain regions. These results suggest that an alteration of dopaminergic neuron activity following a reduction of DA and its metabolites in specific brain regions (e.g., striatum, limbic, midbrain, and pons/medulla) play an important role in the expression of the opioid withdrawal syndrome.     

Systemic administration of CCK-8S, but not CCK-4, enhances dopamine turnover in the posterior nucleus accumbens: a microdialysis study in freely moving rats

The present study was carried out to examine the effects of peripheral administration of sulfatedcholecystokinin octapeptide (CCK-8S) on dopamine (DA) turnover in the posterior nucleus accumbens (PNAc) and the caudate-putamen (CP) in awake rats. Microdialysis was used to quantify the extracellular concentrations of DA and its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Intraperitoneal injections of CCK-8S (0.3 mg/kg b.wt.) caused a significant increase in DOPAC and HVA concentrations in the PNAc, but did not affect the DA level. Such increases in the metabolite contents were not found in the CP. Similar injections of vehicle (1% NaHCO3 solution, 1 ml/kg b.wt.) did not have an effect in either brain region. In an attempt to determine the type of receptor involved in the CCK-8S-induced changes, CCK tetrapeptide (CCK-4, 0.3 mg/kg b.wt.) known to have high affinity for CCKB subtype or vehicle (10% DMSO-saline, 1 ml/kg b.wt.) was administered intraperitoneally. Neither CCK-4 nor vehicle caused significant changes in any of extracellular DA, DOPAC and HVA contents in the PNAc. These results suggest that peripherally administered CCK-8S has stimulatory effects on the dopaminergic system in the PNAc, and raise the possibility that the effect appears to be mediated via CCKA receptors.     

Acute changes in norepinephrine content in the median eminence induced by orchidectomy or testosterone replacement

Median eminence catecholamines were measured in individual samples from intact, castrated, or sham-operated male rats, in order to correlate changes in catecholamine content with the early post-castration rise in serum LH levels. Both norepinephrine (NE) and dopamine (DA) were measured by an enzymatic-isotopic assay and advantage was also taken of a method recently developed that makes it possible to obtain the median eminence free of the surrounding hypothalamus. Determinations were made at 4, 8, or 24 h after surgery. All animals were killed between 1400 and 1600 h. It was observed that castration increases the ME content of NE significantly at all the times studied, with peak values 8 h after orchidectomy. Sham operation induced a significant decrease in NE content in the ME 4 h after surgery. By 8 h the NE values had returned to intact control levels. Both castration and sham operation induced a significant decrease in DA levels 4 h after surgery. By 8 h, DA values had returned to intact control levels in both groups. When the NE levels in castrated rats had reached the highest value, serum LH values had not departed from control levels, indicating that the change in NE content in the ME takes place prior to the expected rise in LH. Testosterone replacement therapy (40 mug/100 gBW) of castrated rats blocked the increase in NE content observed 8 h after castration. Dopamine levels were not affected by this treatment. These results support the concept that the NE contained in median eminence catecholaminergic terminals participates in the feed-back regulation of LH secretion in the male rat, while DA is apparently not involved under the present conditions.     

Changes in dopamine, serotonin and their metabolites in discrete brain areas of rat offspring after in utero exposure to cocaine or related drugs

The concentrations of dopamine (DA), serotonin (5HT) and their metabolites were quantified in 5 brain areas of rats exposed to saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg), or amfonelic acid (AFA, 1.5 mg/kg) throughout gestation. Male pups from 3 similarly treated dams were fostered to 2 surrogate dams. The process of breeding and rearing was repeated 4 times with new dams to build the groups to 4-12, since only one pup per litter was used for any one measurement. AFA was used to mimic the dopamine (DA) uptake blockade and stimulant properties of cocaine and amitriptyline was used to mimic the other pharmacological effects of cocaine. At postnatal days (PND) 30, 60, and 180, one pup per litter was removed for HPLC analysis of monoamines. A second pup received 0.3 mg/kg haloperidol, catalepsy assessed after 1 hr, and the brain used for analysis. The cataleptic response to haloperidol was unaffected by any prenatal treatment. The striatum from PND 30 cocaine rats had decreased levels of DA without a decrease in DA metabolites. At PND 60 in cocaine exposed rats, DA and DOPAC concentrations were increased, and 5HT levels were decreased in the striatum. The amitriptyline-exposed group exhibited decreased 5HT and 5-HIAA levels in the striatum. The hypothalamus of the cocaine group had lower levels of 5-HIAA, and other brain areas had a trend for lower levels of 5HT and 5-HIAA. At PND 180, DOPAC was increased in the striatum and prefrontal cortex of the cocaine group. Haloperidol-induced altered monoamine metabolism was unaffected by any prenatal treatment at any age. These data suggest that age-related changes in the DA and 5HT neurotransmission systems occur in rats exposed prenatally to cocaine. However, the ability of the dopaminergic system to respond to a challenge by a DA receptor blocker is unaltered by these in utero treatments.     

Chromosome structure and composition

Previous studies in rodents showed a severe deterioration of pineal physiology with aging. The present study investigated the age-related changes in the content of monoamines and metabolites in rat and Syrian hamster pineal gland. In addition to melatonin, the levels of 5-hydroxytryptophan (5HTP), serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), N-acetylserotonin (N-Ac-SHT), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and noradrenaline (NA) were measured by HPLC. Pronounced reductions were found in 5HT and 5HIAA contents during daytime in rats of 24 months, which had not been observed in animals of 12 months. In addition, nighttime pineal 5HIAA, N-Ac-5HT, and melatonin contents were decreased in the old rats, although a significant day:night variation persisted. Also a diurnal fluctuation in NA, DA, and DOPAC contents was present in young and middle-aged rats but not for NA and DOPAC in the oldest rats due to a decrease in the nighttime levels. Pineal DA levels were also reduced in 24-month-old rats during the night, although a marked day:night change was still found. In the Syrian hamster pineal, significant reductions in daytime 5HT and 5HIAA were found respectively at 12 and 18 months, while nighttime levels of these compounds were decreased from 18 months. The nocturnal content of N-Ac-5HT dropped gradually from 12 months, and melatonin was reduced by 74% and 86% in hamsters of 18 and 24 months, respectively. In all these compounds, a significant day:night variation was observed irrespective of age. However, neither a day:night variation nor an effect of aging was found in terms of pineal NA content. In contrast, pineal DA and DOPAC levels displayed a diurnal variation in hamsters of 1.5 and 6 months, but not in animals of 12 and 18 months due a reduced nighttime content. These data suggest that the decline of pineal melatonin with age is a consequence of a deficit in the pathway of serotonin utilization. This probably is explained by a reduced N-acetyltransferase activity, which may be linked to impaired pineal catecholaminergic neurotransmission.