Anxiolytic-like effects of a new 1-N substituted analogue of melatonin in pinealectomized rats (883.2) (original) (raw)
Related papers
Anxiolytic-like effects of a new 1-N substituted analog of melatonin in pinealectomized rats
Progress in neuro-psychopharmacology & biological psychiatry, 2014
In spite of the wide variety of drugs available for treating anxiety, this disorder continues to represent a worldwide health problem that is classified within the first 10 causes of disability. Therefore, the search continues for new antianxiety agents, particularly those not related to benzodiazepines. Even though melatonin has been prescribed as an anxiolytic drug, its use is currently limited due to its short half-life and photo-sensitivity, among other disadvantages. The present study explores the antianxiety properties of a new 1-N substituted melatonin analog, M3C, in pinealectomized rats submitted to two behavioral tests (the cumulative burying behavior paradigm and the elevated plus-maze). Results from both tests show that M3C is effective as an anxiolytic-like agent, at doses lower than any other melatonin analog previously reported. The blocking of these actions by luzindole together with the available data suggests that the anxiolytic properties of M3C are mediated by MT...
Melatonin as a Potential Approach to Anxiety Treatment
International Journal of Molecular Sciences
Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin’s benefit in anxiety may reside in its sympatholytic ac...
European Journal of Pharmacology, 1993
Anxiolytic and pro-exploratory melatonin properties were assessed in rats using a plus-maze procedure. Both melatonin (1 mg/kg) and diazepam (0.5 mg/kg) showed a significant diurnal variation to decrease anxiety and to promote exploratory behavior. Melatonin displayed anxiolytic activity at night, with absence of effects at noon and a weak activity at the beginning of the light phase. Melatonin pro-exploratory activity was found only at night. Diazepam exerted significant anxiolysis during the night, with less activity during the day. Diazepam pro-exploratory activity was found during the night only. A dose-response study carried out by injecting 1-20 mg/
Behavioural actions of two new 1-N substituted analogues of melatonin
Behavioural Brain Research, 2013
In two animal models of anxiety, two 1-N melatonin analogues show better effects than the original molecule. Two new 1-N analogues produce sedative effects that last several hours. MT and its 1-N analogues reduce the seizures induced by pentylenetetrazole.
Behavioural Brain Research, 2011
In the present study, the effects of intraamygdalar administrations of melatonin (1 and 100 g/kg), saline and diazepam on the anxiety-like behavior and spatial memory performance in pinealectomized and sham-pinealectomized Wistar rats were investigated. The animals were tested by open field and elevated plus maze tests for anxiety-like behavior, and Morris water maze test for spatial memory. In open field, (a) diazepam was more effective in reducing the anxiety, (b) control subjects were more mobile than pinealectomized subjects and (c) 100 g/kg melatonin administrations reduced the velocity of the animals. In elevated plus maze, (a) 100 g/kg melatonin administrations increased the distance totally travelled and (b) enhanced the time spent in open arms, however, after the pinealectomy, 1 g/kg melatonin administrations decreased it and (c) control animals were less mobile than pinealectomized ones. In Morris water maze, (a) diazepam group travelled more distance than the others in control condition whereas, in pinealectomy condition high dose of melatonin and saline groups travelled more distance than the others, (b) in pinealectomy condition subjects who received 100 g/kg melatonin also travelled more distance than those who received 1 g/kg melatonin and diazepam, (c) the subjects who received 1 g/kg spent less time than those who received other treatments, and (d) in control condition subjects who received 100 g/kg melatonin were slower than those who received the other treatments. In conclusion, melatonin administration to amygdala decreased the anxiety; however, spatial memory performance of the rats was impaired by the pinealectomy and melatonin administrations.
Neuroscience and Medicine, 2012
The main objective of this work was to 1) study the influence of endogenous melatonin (Mel) abolishment via pinealectomy and 2) explore exogenous Mel effect on anxiety-like and depressive-like behavior in male and female rats. Rats were shamoperated (Sh) or pinealectomized (Px) and following subgroups were selected 1) Px/NaCl (0.9%) and Sh/NaCl (0.9%) : rats injected subcutaneously, once daily for 8 weeks, with saline solution NaCl (0.9%) as vehicle; 2) Px/Mel (4 mg/Kg) and Sh/Mel (4 mg/Kg): rats similarly injected with 4 mg/Kg of Mel. All animals were housed under a photoperiod of (LD:16/8). After different treatments animals were tested in the open-field test (OFT), elevated plus maze test (EPM) to determine anxiety-like behavior, and forced swimming test (FST) to evaluate depressive-like level. Our results revealed that level of anxiety-like and depressive-like behavior are significantly higher in Px/NaCl (0.9%) when compared to Sh/NaCl (0.9%) group, suggesting that pinelectomy induced an anxiogenic and depressant effects. The Px effects would be due to the absence of endogenous Mel synthesis and release. Additionally, we clearly demonstrated that the level of anxiety-like and depressive-like behavior are higher in Px/Mel (4 mg/Kg) and Sh/Mel when compared respectively to Px/NaCl (4 mg/Kg) and Sh/NaCl groups suggesting an anxiolytic and antidepressant effects of exogenous Mel. Behavioral responses were sex dependent since the difference between females and males, especially, after melatonin administration, were statistically significant. These experiments provide evidence that pinealectomy and Mel regulated emotionally behavior in male and female rats.
Anxiolytic-like action of melatonin on acquisition but not performance of DRL
Pharmacology Biochemistry and Behavior, 1986
PHARMACOL BIOCHEM BEHAV 24(6) [1497][1498][1499][1500][1501][1502] 1986.---The behavioural effects of melatonin have been attributed to a general reduction in motor activity; interference with memory fixation; a decrease in emotionality; or an anxiolytic action. The present experiments compared the effects of melatonin with an anxiolytic benzodiazepine, chlordiazepoxide (Librium), on a schedule of differential reinforcement of low rates of response (DRL) increasing 'burst' responding and premature responding. No doses of melatonin tested (0.03-8.1 mg/kg, IP) affected performance of well-learned DRL. Both low (0.03 mg/kg) and high (1.0 mg/kg) doses of melatonin impaired acquisition of DRL in a similar manner to chlordiazepoxide (5.0 mg/kg) and to much the same extent. Chlordiazepoxide had its usual effects on both acquisition and performance of DRL. These results show that melatonin shares a subset of the effects of chlordiazepoxide. The nature of the effects favours an 'anxiolytic' hypothesis of melatonin action rather than the other hypotheses so far proposed.
Melatonin agonists for treatment of sleep and depressive disorders
Journal of Experimental and Integrative Medicine, 2011
Melatonin the hormone secreted by the pineal gland has been effective in improving sleep both in normal sleepers and insomniacs and has been used successfully in treating sleep and circadian rhythm sleep disorders. The lack of consistency in the reports published by the authors is attributed to the differential bioavailabilty and short half-life of melatonin. Sleep disturbances are also prominent features of depressive disorders. To overcome this problem, melatonergic agonists with sleep promoting properties have been introduced in clinical practice. Ramelteon, the MT1/ MT2 melatonergic agonist, has been used in a large number of clinical trials involving chronic insomniacs and has been found effective in improving the total sleep time and sleep efficiency of insomniacs and has not manifested serious adverse effects. The development of another MT1/MT2 melatonergic agonist agomelatine with antagonsim to 5-HT2c serotonin receptors has been found useful not only in treating sleep problems of patients but also as a first line antidepressant with earlier onset of actions in patients with major depressive disorder. An agonist for MT3 melatonin receptor has also been found effective in animal models of depression.
Journal of Pineal Research, 1990
A naturally occurring compound, 6-methoxybenzoxazolinone (6-MBOA), present in grasses, has been shown to induce sexual maturation in a number of rodent species. The structural similarity of 6-MBOA and melatonin has led researchers to suspect that 6-MBOA might induce its progonadal effects by directly altering pineal function. Previous studies have shown that 6-MBOA has the properties of a weak β-adrenergic agonist capable of stimulating rat pineal N-acetyltransferase (NAT) activity at pharmacological concentrations of 10−3 M. In the present study we have examined the effect of 6-MBOA on both the pineal melatonin synthesizing enzymes, namely. NAT and hydroxyindole-O-methyltransferase (HIOMT) as well as on melatonin production, in organ cultured rat pineal glands. In addition, we have also examined the ability of 6-MBOA to displace a ligand from rat brain α-and β-adrenoceptors. Our results confirm that 6-MBOA stimulates NAT activity and melatonin production at the high concentration of 10−3 M. It appears to have no effect on HIOMT activity. A competition study shows that 6-MBOA is able of displacing ligands at the α-and β-adrenoceptors but only at concentrations greater that 10−4 M. Whether such high concentrations of 6-MBOA reach the pineal of rodent in their natural habitat is unknown. However, if 6-MBOA does mediate progonadal effects by altering pineal function it would be expected that 6-MBOA would ultimately inhibit the effects of melatonin. The possibilities are that the high melatonin levels induced by 6-MBOA cause desensitization of melatonin receptors or that 6-MBOA is an antagonist at the level of the melatonin receptor, thus restricting the inhibitory effects of melatonin on the reproductive system.