Agmatine Inhibits Behavioral Sensitization to Ethanol Through Imidazoline Receptors.

Background: Locomotor sensitization to repeated ethanol (EtOH) administration is proposed to play a role in early and recurring steps of addiction. The present study was designed to examine the effect of agmatine on EtOH-induced locomotor sensitization in mice.

Methods: Mice received daily single intraperitoneal injection of EtOH (2.

Agmatine inhibits nicotine withdrawal induced cognitive deficits in inhibitory avoidance task in rats: Contribution of α-adrenoceptors.

Nicotine abstinence following chronic exposure is associated with impairments in memory and variety of cognitive functions. Daily nicotine (2 mg/kg, sc, four times daily) administration for 14 days and its abrupt withdrawal significantly impaired avoidance learning in inhibitory avoidance task as indicated by a significant decrease in the step through latency. Animals injected with agmatine (10-40 μg/rat, icv) from day 7 to 14 before the first daily dose of nicotine (2 mg/kg, sc) showed increased step through latencies during retrieval test.

Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis.

Agmatine attenuates hyperactivity and weight loss associated with activity-based anorexia in female rats.

Anorexia nervosa is a debilitating eating disorder characterized by hypophagia, body weight loss, amenorrhea and intense fear of weight gain. In present study, the effect of subchronic agmatine treatment on development of activity based anorexia (ABA) in female rats has been investigated. Animals were injected with saline or agmatine (10-40 mg/kg, ip) just before the onset of dark phase and shifted to experimental cage with wheel for ABA test for 10days.

Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c.

Agmatine attenuates lipopolysaccharide induced anorexia and sickness behavior in rats.

Sickness behavior is characterized by lethargy, reduced appetite, anhedonia and anxiety. It can be induced in experimental animals by bacterial endotoxin, lipopolysaccharide (LPS). We investigated the impact of intracerebroventricular agmatine injections (5-20μg/rat, icv) on sickness behavior induced by LPS (100μg/rat, ip) in rats.

Neuropeptide Y in the central nucleus of amygdala regulates the anxiolytic effect of agmatine in rats.

In the present study, modulation of anxiolytic action of agmatine by neuropeptide Y (NPY) in the central nucleus of amygdala (CeA) is evaluated employing Vogel's conflict test (VCT) in rats. The intra-CeA administration of agmatine (0.6 and 1.

Participation of central imidazoline binding sites in antinociceptive effect of ethanol and nicotine in rats.

Despite synergistic morbidity and mortality, concomitant consumption of alcohol and tobacco is increasing, and their antinociceptive effect has been linked with co-abuse. Present study was designed to investigate the role of imidazoline binding sites in the antinociceptive effect of nicotine, ethanol, and their combination. Separate group of male Sprague-Dawley rats (200-250 g) were treated with different doses of alcohol (0.

Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test.

Although bupropion has been widely used in the treatment of depression, the precise mechanism of its therapeutic actions is not fully understood. The present study investigated the role of agmatine in an antidepressant like effect of bupropion in mouse forced swim test. The antidepressant like effect of bupropion was potentiated by pretreatment with agmatine (10-20mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz.

Neurosteroid allopregnanolone attenuates development of nicotine withdrawal behavior in mice.

Avoidance of the nicotine withdrawal syndrome as well as the positive subjective effects of nicotine is the major predisposing factor to motivate nicotine abuse. However, its underlying neurobehavioral mechanisms remain perplexing. In the present study, we investigated the influence of the neurosteroid allopregnanolone (ALLO; 0.

Psychopharmacological study of agmatine in behavioral tests of schizophrenia in rodents.

The effect of agmatine in preclinical behavioral tests of schizophrenia has been examined in rodents. Agmatine at the doses of 40 and 80 mg/kg blocked conditioned avoidance responding, attenuated apomorphine induced climbing, diminished amphetamine and ketamine hyperlocomotor activity and augmented plasma prolactin levels. Pretreatment of animals with 20 mg/kg of agmatine potentiated the inhibitory effect of haloperidol (0.

Repeated agmatine treatment attenuates nicotine sensitization in mice: modulation by alpha2-adrenoceptors.

Agmatine [2-(4-aminobutyl)guanidine] is an endogenous amine proposed as a neurotransmitter/neuromodulator that binds to multiple target receptors in brain. Besides, many central and peripheral functions, agmatine have been implicated in the process of drug addiction. The purpose of the present study was to examine the effects of centrally injected agmatine on nicotine induced locomotor sensitization in Swiss male mice.

Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats.

Present study investigated the role of agmatine in ethanol-induced anxiolysis and withdrawal anxiety using elevated plus maze (EPM) test in rats. The anxiolytic-like effect of ethanol was potentiated by pretreatment with imidazoline I(1)/I(2) receptor agonist agmatine (10-20 mg/kg, i.p.

Tolerance to ethanol sedation and withdrawal hyper-excitability is mediated via neuropeptide Y Y1 and Y5 receptors.

Aims: Neuropeptide Y (NPY) is widely distributed throughout the brain and has been implicated in some of the actions of ethanol. The aim of the present study was to characterize the subtypes of NPY receptors in ethanol induced sedation, tolerance and withdrawal hyper-excitability.

Main Methods: The loss of righting reflex paradigm was used to record the sleep duration in mice.

Antidepressant like effect of selective serotonin reuptake inhibitors involve modulation of imidazoline receptors by agmatine.

Recent findings demonstrated the dysregulation of imidazoline receptor binding sites in major depression and their normalization by chronic treatment with antidepressants including selective serotonin reuptake inhibitors (SSRIs). Present study investigated the role of agmatine and imidazoline receptors in antidepressant like effect of SSRIs and imipramine in mouse forced swimming test (FST) paradigm. The antidepressant like effect of fluoxetine or paroxetine was potentiated by imidazoline I(1)/I(2) receptor agonist agmatine (5-10 mg/kg, ip), imidazoline I(1) receptor agonists, moxonidine (0.

Involvement of alpha-melanocyte stimulating hormone (alpha-MSH) in differential ethanol exposure and withdrawal related depression in rat: neuroanatomical-behavioral correlates.

We investigated the involvement of alpha-melanocyte stimulating hormone (alpha-MSH) following acute, chronic and withdrawal treatments of ethanol with reference to depression. The degree of depression was evaluated using Porsolt's forced swim test. While intracerebroventricular (i.

Neurosteroid allopregnanolone mediates anxiolytic effect of etifoxine in rats.

Etifoxine (6-chloro-2-ethylamino-4-methyl-4-phenyl-4H-3,1-benzoxazine hydrochloride), a nonbenzodiazepine anxiolytic drug, potentiates GABA(A) receptor function perhaps through stimulation of neurosteroid biosynthesis. However, the exact mechanism of etifoxine action is not fully understood. In this study, we have assessed the possible role of GABAergic neurosteroid like allopregnanolone (ALLO) in the anxiolytic-like effect of etifoxine in rats using elevated plus maze test.

Central administration of selective melanocortin 4 receptor antagonist HS014 prevents morphine tolerance and withdrawal hyperalgesia.

Major problem involved in treatment of chronic pain with morphine is the development of tolerance and dependence. Previous studies have demonstrated the participation of melanocortin (MC) system in the development of tolerance to antinociceptive effect of morphine. However, the impact of supraspinal MC4 receptors (MC4 R) modulation on this phenomenon and morphine withdrawal hyperalgesia remained unexplored.

Chronic progesterone treatment augments while dehydroepiandrosterone sulphate prevents tolerance to ethanol anxiolysis and withdrawal anxiety in rats.

We have recently shown that the neurosteroid allopregnanolone modulates anxiolytic effect of ethanol. In the present report, we attempted to examine whether neurosteroids progesterone and dehydroepiandrosterone sulphate (DHEAS), which modulate gamma-aminobutyric acid (GABA(A)) receptor function, affects development of tolerance to ethanol anxiolysis and withdrawal anxiety. Rats on ethanol (6% v/v in nutritionally balanced liquid diet) for prolong period (10 days) were injected twice daily either with vehicle, progesterone (a precursor of allopregnanolone, positive GABA(A) receptor modulator), finasteride (5alpha-reductase inhibitor) or DHEAS (negative GABA(A) receptor modulator).

Alpha-melanocyte stimulating hormone antagonizes antidepressant-like effect of neuropeptide Y in Porsolt's test in rats.

The physiological and functional interaction between neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alpha-MSH) with reference to anxiety and food intake is well documented. An attempt has been made to study the influence of melanocortin (MC) system on NPY induced antidepressant-like effect in rats using Porsolt's forced swim test as the behavioral paradigm. NPY (0.

Participation of alpha-melanocyte stimulating hormone in ethanol-induced anxiolysis and withdrawal anxiety in rats.

Although recent reports underscore a close association between the ethanol consumption and the central melanocortin (MC) system in rats, neurobehavioral component of this association has not been explored. In this study, we investigated the role of alpha-melanocyte stimulating hormone (alpha-MSH) in ethanol (1.5-2 g/kg, i.

GABA(A) receptors mediate orexin-A induced stimulation of food intake.

Although the role of orexins in sleep/wake cycle and feeding behavior is well established, underlying mechanisms have not been fully understood. An attempt has been made to investigate the role of GABA(A) receptors and their benzodiazepine site on the orexin-A induced response to feeding. Different groups of rats were food deprived overnight and next day injected intracerebroventricularly (icv) with vehicle (artificial CSF; 5 microl/rat) or orexin-A (20-50 nM/rat) and the animals were given free access to food.

Interaction between neuropeptide Y and alpha-melanocyte stimulating hormone in amygdala regulates anxiety in rats.

Neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alpha-MSH) have been implicated in pathophysiology of feeding and certain mood disorders, including anxiety and depression. Both the peptides are abundantly present in CNS, especially in the hypothalamus and amygdala. Although they are known to exert opposite effects, particularly with reference to anxiety, the underlying mechanisms are not known.

Evaluation of GABAergic neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one as a neurobiological substrate for the anti-anxiety effect of ethanol in rats.

Rationale: Acute systemic ethanol administration is known to elevate plasma and cerebral levels of neuroactive steroid 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha, 5alpha-THP; allopregnanolone) to a concentration sufficient to potentiate GABA(A) receptors. We have earlier demonstrated that 3alpha, 5alpha-THP mediates the antidepressant-like effect of ethanol in Porsolt forced swim test.

Objective: The aim of the present study is to explain the relationship between endogenous GABAergic neurosteroids and anxiolytic effect of ethanol in Sprague-Dawley rats.

Essentiality of central GABAergic neuroactive steroid allopregnanolone for anticonvulsant action of fluoxetine against pentylenetetrazole-induced seizures in mice.

Fluoxetine, a selective serotonin reuptake inhibitor, is known to increase the cortical content of allopregnanolone (ALLO) without altering the level of other neurosteroids. In contrast to the proconvulsant effect of many antidepressants, fluoxetine exhibits anticonvulsant effects. The present study was undertaken to examine the role of ALLO in the anticonvulsant action of fluoxetine against pentylenetetrazole (PTZ)-induced seizures in mice.