Search

Nanoparticles are now widely used in various aspects of life, especially zinc oxide nanoparticles (ZnNPs) that used in mouth washing, cosmetics, sunscreens, toothpaste and root canal flings. This research aims to determine the impact of ZnNPs on healthy mice's brain tissue. ZnNPs have caused major changes in the brain monoamines (dopamine, norepinephrine and serotonin) and ions such as Ca2+, Na+, K+ and Zn2+. Concerning the histological picture, administration of ZnNPs caused some histopathological impairment in brain tissue. In addition, ZnNPs reduced the level of glutathione and catalase in brain tissue, although an increase in the level of nitrite / nitrate and ROS was observed, while the level of malondialdhyde was not significantly altered. Moreover, ZnNPs induced DNA fragmentation in brain of mice. Collectively, the obtained results revealed that ZnNPs affected the brain levels of investigated monamines, ions, enzymatic and non-enzymatic antioxidants thus they may have potential influence on central nervous system.

Pain-associated depression is encountered clinically in some cases such as cancer, chronic neuropathy, and after operations. Tramadol is an opioid analgesic drug that may modulate monoaminergic neurotransmission by inhibition of noradrenaline and serotonin reuptake that may contribute to its antidepressant-like effects. Clinically, tramadol is used either alone or in combination with other NSAIDs in the treatment of cases associated with pain and depression, e.g. low back pain, spinal cord injury, and post-operative pain management. However, tramadol monotherapy as an antidepressant is impeded by severe adverse effects including seizures and serotonin syndrome. Interestingly, phosphodiesterase-III inhibitors demonstrated novel promising antidepressant effects. Among which, cilostazol was reported to attenuate depression in post-stroke cases, geriatrics and patients undergoing carotid artery stenting. Therefore, this study was carried out to investigate the possible antidepressant-like effects of tramadol and/or cilostazol on the behavioral level in experimental animals, and to examine the neurochemical and biochemical effects of tramadol, cilostazol and their combination in rats, in order to explore the probable mechanisms of action underlying their effects. To achieve our target, male albino mice and rats were randomly allocated into five groups and administered either vehicle for control, fluoxetine (20 mg/kg, p.o.), tramadol HCl (20 mg/kg, p.o.), cilostazol (100 mg/kg, p.o.), or combination of both tramadol and cilostazol. At day 14, mice and rats were challenged in the tail suspension test and forced swim test, respectively. Rats were sacrificed and brains were isolated for determination of brain monoamines, MDA, NO, SOD, and TNF-α. The current results showed that concurrent administration of cilostazol to tramadol-treated animals modulated depression on the behavioral level, and showed ameliorative neurochemical and biochemical effects in rats exposed to FST.

The presence of blue or red-brown substrate on the tank bottom has been previously reported as an efficient means of environmental enrichment for gilthead seabream. The present study aimed to investigate whether this enrichment is still beneficial when gilthead seabream is reared under different social conditions (i.e. a lower 4.9 kg m − 3 and a higher 9.7 kg m − 3 density). Water exchange was adjusted according to fish biomass to exclude density effects on water quality. In the enriched tanks single-colour glass gravel was used as substrate (blue and red-brown substrate, or BS and RBS respectively), while control tanks had no gravel. Growth, aggressive behaviour and size distribution results indicated that the lower density created a less favourable social environment. In both densities studied, BS enhanced growth, suppressed aggression and reduced brain serotonergic activity. In the condition of intense social interactions (i.e. the lower density) BS also reduced brain dopaminergic activity. These results along with the negative correlations observed between brain monoamines and fish body mass, indicated that substrate and density effects are socially-induced. However, there may be several biotic and/or abiotic factors interfering with substrate effects that should be investigated before the practical use of a substrate in land-based intensive aquaculture.

1. By study of the synthesis and turnover of brain monoamines and with the use of behavioral models which indicate the functional activity of brain 5HT and dopamine, it is possible to unravel the mechanisms by which some drugs produce behavioral effects. 2. Using these techniques the acute and chronic effects of certain neuroleptics, propranolol and other beta-adrenergic blocking agents, repeated electroconvulsive shock, and lithium upon the functional activity of brain 5HT and dopamine are examined. 3. The clinical relevance of these studies is discussed.

The effects of i.v. injected delta9-tetrahydrocannabinol (delta9-THC) on behaviour, body temperature and levels of brain monoamines, measured spectrophotofluorimetrically, of the rat were determined. Doses of delta9-THC in the range of 0.05--5.0 mg/kg produced biphasic changes in behaviour, body temperature and levels of 5-hydroxyindoleacetic acid (5-HIAA). The whole brain levels of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were not altered by delta9-THC. The subjective behavioural biphasic responses did not appear to be dose related, whereas the biphasic changes in body temperature and brain levels of 5-HIAA were dose-related. Low doses of delta9-THC (0.05 and 0.1 mg/kg) caused hyperthermia, while doses of 1.0, 2.0 and 5.0 mg/kg induced hypothermia. On the other hand, 0.05 mg/kg delta9-THC significantly reduced, whereas doses of 1.0, 2.0 and 5.0 mg/kg significantly increased the 5-HIAA levels in a dose-related manner. It is concluded that an inverse relationship exists between delta9-THC-induced changes in body temperature and alterations in brain 5-HIAA levels.

(1) Serum TSH responses to TRH showed abnormal patterns in terms of diminished, delayed and exaggerated responses in more than one third of the depressed patients. (2) These findings suggest the pathogenetic importance of the hypothalamo-pituitary dysfunction in depressed patients. Because of this, a number of patients, especially those with diminished and delayed TSH responses to TRH, are prone to develop latent hypothyroidism which might make them resistant to antidepressants. (3) To elucidate the underlying mechanism of these clinical findings, changes in brain monoamines of ‘depression model rats’ were examined by the histochemical fluorescence method. (4) Fluorescence intensity in nerve cells of the ascending NA system (A1, A2, A5, A6, A7) was markedly increased and fluorescence intensity in cell bodies (A12) and nerve terminals (ext. ME) of the tubero-infundibular DA system was decreased.

The effect of reserpine on dopamine, noradrenaline, adrenaline and serotonin concentrations in different brain regions, and the recovery of normal levels of these monoamines after such treatment were studied in rats aged 5, 15 and 27 months. In a preliminary experiment we found that distribution of the drug was not altered in the aged rats. Then we observed that a single dose of reserpine (5 mg/kg IP) had a similar depleting effect on all the brain monoamines, in all the brain regions considered in all three age groups. The curves expressing recovery of monoamine storage in all the nerve terminals, several days after treatment, were superimposable. These results suggest that in the rat, age does not influence the effect of reserpine on the storage mechanism of brain monoamines. Moreover, as restoration of this mechanism depends on the synthesis of new vesicles, the similarity in the rates of recovery in adult, old and very old rats indicated indirectly that synthesis of these neuronal organelles is not affected by aging.

Mouse-killing by rats is blocked by chronic administration of electroconvulsive shock. Antidepressive drugs also block mouse-killing by rats. Thus, mouse-killing by rats may be under the control of mechanisms analogous to human depression. Whole brain concentrations of norepinephrine were higher in rats that received ECS.

Summary 5,7-Dihydroxytryptamine (12.5, 25.0, or 50.0 μg) was injected intracisternally in male and female rats at birth; animals were killed 3, 12, 24, or 60 days after the injections and brain monoamines were examined for changes in the concentrations of various neurotransmitters. Brain serotonin levels were markedly depleted at all time periods examined, with the greatest reduction occurring after the injection of 50 μg of the drug. In animals killed at 60 days of age, decreases also occurred in the concentrations of brain and spinal cord 5-hydroxyindoleacetic acid and brain norepinephrine, although the depressions in brain norepinephrine were small (73% of controls) and non-dose related. Spinal cord, and regional and whole brain levels of serotonin and 5-hydroxyindoleacetic acid were still decreased 120 and 240 days after injection. Whereas brain norepinephrine was also depressed at 240 days of age, brain levels of tryptophan or dopamine, and cardiac levels of norepinephrine, were unchanged.

Castrated male rats treated daily with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA, 20 mg/kg) started to display mounts, intromissions and ejaculations more rapidly in response to daily treatment with testosterone propionate (TP, 0.15 mg/kg) than NaCl-treated rats. Daily treatment with the catecholamine (CA) synthesis inhibitor α-methyl-p-tyrosine (α-MT, 20 mg/kg) had no effect on the behavioral response to subsequent TP treatment. The acceleration of TP-induced sexual behavior by PCPA pretreatment was inhibited by pretreatment with DL-5-HTP (20 mg/kg) but not with L-DOPA (12.5 mg/kg). Analyses of brain monoamines showed that the PCPA treatment reduced brain 5-HT levels and produced a marked inhibition of the 5-HT synthesis. The 5-HTP treatment restored brain 5-HT levels to normal. Daily treatment with PCPA also reduced brain CA levels and inhibited the CA synthesis but these biochemical effects were not related to the effects of PCPA on sexual behavior. Daily treatment with PCPA (40 mg/kg for 12 days) or treatment with 126 mg/kg PCPA for 3 days induced the complete pattern of sexual behavior in 5 of 9 and 19 of 30 castrated rats respectively without concurrent TP treatment. It is suggested that 5-HT exerts a modulating influence on sexual behavior in male rats.

The effects of high pressure on the whole brain concentrations of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), and noradrenaline (NA) were determined in the mouse. Application of high pressure (over 100atm) elevated the brain 5-HIAA concentrations but had little or no influence on the concentrations of 5-HT, DA, or NA. The pressure-induced increase in 5-HIAA was still present after the administration of the monoamine-depleting drugs, parachlorophenylalanine (PCPA), α -methyl- p -tyrosine (α-MPT), reserpine, and FLA-63. Reserpine (4 mg/kg) and FLA-63 (50mg/kg) lowered the pressure at which tremors, convulsions, and death occurred. In contrast, PCPA (3 doses of 300 mg/kg) and α-MPT (2 doses of 250 mg/kg) did not alter the threshold pressures for the behavioural end-points in the high pressure neurological syndrome. Thus, the depletions of 5-HT or of DA and NA alone do not seem to affect the response to pressure, and it may be that alterations in tremor and convulsion threshold pressures are dependent upon a balance of all the monoamine neurotransmitter systems. The involvement of monoamines in the high pressure neurological syndrome resembles to some extent their postulated roles in electroshock, pentylenetetrazol and auditory convulsions.

Two strains of mice (C57BL/6J and DBA/2J) were used to determine the effects of single and multiple injections of methadone on open field activity and on brain monoamines. For the DBA strain, the initial injection of methadone produced an attenuation of locomotor activity. After 7 daily injections, activity increased to that of controls. For the C57 strain, the initial injection produced a slight increase in activity which became more pronounced after further daily injections. Norepinephrine concentration was elevated in brains of DBA mice chronically exposed to methadone. This effect was not observed in C57 mice nor in either strain injected only once with the drug. Serotonin concentration was not altered in animals of either strain whether acutely or chronically exposed to methadone. The results of this study suggest: 1) that activity change following methadone injections is dependent upon genetic factors and previous experience with the drug; 2) that the tolerance develops to the drug produced decreases but not increases in activity; and 3) that chronic exposure to the drug can elevate norepinephrine concentration in the brains of DBA mice.

1. 1. The interactions between cholecystokinin (CCK) and brain monoamines have been investigated. The data found in the literature are quite dissimilar. 2. 2. Several reasons for these disparities have been suggested. We have sought to test some of them, such as the strain of rat, the nutritional state (by the use of two models of obesity), the length of the peptide (CCK 8 and CCK 33), the route of administration (i.p. and i.c.v.) and the time of sacrifice. 3. 3. We indeed found all these experimental conditions to be the cause of differential effects on brain monoamines and metabolites. 4. 4. However, by repeating the same experiments several times, we did not always obtain the same variations, even under the same conditions. In addition to the different parameters tested, another source of variability exists, possibly due to the molecule itself or to seasonal variations.

The relative importance of brain monoamines for behavior maintained by a fixed-ratio 30 schedule of food reinforcement was evaluated using drug regimens designed to preferentially prevent reserpine-induced depletion of catecholamines, of 5-hydroxytryptamine (5-HT), or of all 3 monoamines. In all regimens the animals were studied 24 hr after reserpine. A severe depression of lever-pressing was observed in mice in which monoamines were depleted by 2.5 mg/kg reserpine alone and those in which catecholamine content was reduced but 5-HT maintained at control levels by injections of 200–400 mg/kg DL-5-hydroxytryptophan before and after reserpine treatment. Injections of 300–400 mg/kg L-dopa prior to and after reserpine prevented depletion of catecholamines whereas central 5-HT content dropped to 62% control. Following this regimen, mice showed a slight but significant decrease in lever-pressing rate. Pre-reserpine administration of 200 mg/kg tetrabenazine maintained dopamine and 5-HT levels at 76–77% with norepinephrine dropping to 56% control. Despite this partial depletion of monoamine stores, tetrabenazine-protected mice displayed no change in their post-injection lever-pressing performance. We conclude that catecholamines are necessary for conditioned lever-pressing but that 5-HT may play a contributory role. Further, the ratio of brain monoamine levels may be an important correlate of fixed-ratio performance.

The reaction of painful stimulation was studied in rats by means of three different techniques. Lesions of the midbrain raphe in rats, which reduced the levels of brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) decreased the analgesic activity of morphine. In some tests, an increase in sensitivity to painful stimulation was noted in lesioned animals. The results obtained support the view that a decrease of brain 5-HT concentration antagonizes morphine analgesia. The possible role of the other brain monoamines in the analgesic activity of morphine is also discussed.

Unilateral olfactory bulb lesions in the rat caused a selective decrease and increase of norepinephrine in the telencephalon and the brainstem, respectively. There were no changes in the concentration of dopamine or serotonin in the ipsilateral telencephalon or brainstem of rats with unilateral lesions. The increase in brainstem norepinephrine concentration in animals with olfactory bulb lesions was reduced when the animals were kept 5 to a cage post-operatively, rather than in isolation.

After exposure of rats to cold-stress, drum-stress, or electric shock-stress, the intraperitoneal LD50 of d-amphetamine was found to be 34.5, 6.1, and 0.9 mg/kg, respectively, in contrast to an LD50 value of 63.5 mg/kg in nonstressed animals. None of the stresses used significantly altered the level of brain stem norepinephrine. However, these levels fell more rapidly after the injection of l -α-methyltyrosine in stressed animals than in nonstressed controls, suggesting a faster turnover rate of this amine. A significant increase in the level of brain stem serotonin was obtained following drum- or electric shock-stress, but not after cold-stress. This increase was obtained in animals subjected to stress alone, or those given the highest possible nonlethal dose of amphetamine. These same doses did not augment the catecholamine-releasing properties of amphetamine in drum- or electric shock-stressed animals. It does not appear that stress potentiates the effects of amphetamine, as no evidence of excitation was obtained in stressed animals given amphetamine. It is postulated that amphetamine enhances the effects of stress. The interrelationships with chlorpromazine, dibenamine, tetrabenazine, chlordiazepoxide, and l -α-methyltyrosine are presented.

1. 1. Experiments with reserpine on Xenopus of different background histories suggest that long-term exposure to a white background leads to a depletion of MSH in the pars intermedia. 2. 2. A model involving the brain monoamines (serotonin and catecholamines) for the control of the pars intermedia is proposed. 3. 3. This follows an explanation for the MSH-releasing effect of reserpine observed by various authors. 4. 4. A possible ACTH-releasing effect of reserpine in Xenopus is also considered.

Lesions were made bilaterally in the lateral hypothalamus in ten rats and in the posteromedial hypothalamic midbrain transition in ten rats. A control group of ten rats had electrodes passed and withdran without any current. The groups of rats were given 12 min of escape conditioning in an operant conditioning situation. The telencephalon was analyzed for 5-hydroxytryptamine (5-HT) and norepinephrine (NE). Brain stems were examined microscopically for lesion site. There was a significant correlation between: (1) low 5-HT and NE in the telencephalon and both lesions, and (2) between prolongation of the escape latency and low 5-HT and NE in telencephalon with a significant difference from control rats, (P

Brain levels of norepinephride, dopamine and serotonin were measured in isolated and aggregated mice after lethal doses of morphine. Although morphine significantly lowered all three brain monoamines there were no significant differences between isolated and aggregated mice. Measurements of brain morphine concentrations also failed to demonstrate any differences which could account for the difference in lethality observed in isolated and aggregated mice.

Since S-adenosylmethionine (SAM) was identified as the most important methyl donor in the body by Cantoni et al. in 1951, various physiological actions have been shown for this substance. Among the various physiological actions of SAM, the effects on phospholipid metabolism, i.e. facilitative effects on phosphatidylcholine biosynthesis and on the metabolism of physiologically active brain amines. This report shows the effects of SAM in healthy animals determined using parameters such as spontaneous motor activity, levels of brain monoamines glucose, glucose-metabolites relating substances,ATP and phospholipids, in comparison with CDP-choline. these substances were injected intravenously or intraperitoneally. An injection of SAM at over 10mg/kg resulted in a slight increase in spontaneous motor activity, but CDP-choline caused no change. An inclination to awake was observed in spontaneous EGG with both of these substances. Regarding brain-monoamines related substance, DA tended to be increased with CDP-choline of over 50mg/kg, and tendencies for increases of HVA and 5-HIAA were observed with SAM of over 10mg/kg.