Abstract
BackgroundDrug withdrawal syndrome occurs due to abrupt cessation of an addictive substance. Dependence to diazepam can be manifested by withdrawal syndrome which may include symptoms such as irritability, psychosis, sleep disturbance, seizures, mood disturbance, and anxiety. Studies have described the therapeutic role of agmatine in various neurological disorders such as depressive mood, learning deficits, anxiety, memory impairment, and psychosis. Various studies have also validated agmatine as a putant neuromodulator and revealed its mechanism of action with other neurotransmitters. The study was designed to reveal the potentials of agmatine in benzodiazepine withdrawal syndrome by maintaining GABA/glutamate balance. The study aimed to determine the underlying mechanism of action of agmatine at synaptic level using behavioral and biochemical evaluations.ResultsAgmatine significantly enhanced locomotion in open filed test and decreased anxiety as observed in elevated plus maze test (p < 0.01). Agmatine also reduced withdrawal symptoms scores along with compulsive behaviors in marble burying test and improved muscular strength by decreasing latency to fall in inverted screen test (p < 0.01). Moreover, agmatine established GABA/glutamate balance by increasing GABA levels and decreased glutamate concentration significantly (p < 0.01).ConclusionThe present study reveals the possible mechanism of action of agmatine on NMDA receptor at GABA interneurons and glutamate post synaptic neuron that may lead to GABA/glutamate balance during withdrawal syndrome.
Highlights
Drug withdrawal syndrome occurs due to abrupt cessation of an addictive substance
3.1 Open field test 3.1.1 Total square crossed Data in Fig. 2a was analyzed by II-way Analysis of variance (ANOVA) that explained the significant effects of days (F (1, 55) = 242.413, p < 0.05), days × drugs (F (3, 55) = 73.552, p < 0.01), days × treatment (F (1, 55) = 14.644, p < 0.25), drugs (F (3, 55) = 34.082, p < 0.01), and treatment (F (1, 55) = 76.117, p < 0.10)
Post hoc analysis determined increased time spent in agmatine-treated animals after the 1st (p < 0.05) and 7th (p < 0.01) administration in water-pretreated controls while in withdrawal animals after the 7th (p < 0.01) administration when compared with water controls, respectively
Summary
Drug withdrawal syndrome occurs due to abrupt cessation of an addictive substance. Dependence to diazepam can be manifested by withdrawal syndrome which may include symptoms such as irritability, psychosis, sleep disturbance, seizures, mood disturbance, and anxiety. Studies have described the therapeutic role of agmatine in various neurological disorders such as depressive mood, learning deficits, anxiety, memory impairment, and psychosis. Various studies have validated agmatine as a putant neuromodulator and revealed its mechanism of action with other neurotransmitters. The study was designed to reveal the potentials of agmatine in benzodiazepine withdrawal syndrome by maintaining GABA/glutamate balance. The study aimed to determine the underlying mechanism of action of agmatine at synaptic level using behavioral and biochemical evaluations. Discontinuation of various drugs or addiction of any interconnecting substance determines the withdrawal syndrome accurately. The functional interaction of agmatine and α2-adrenoceptors has important inhibitory effects on nicotine induced behavioral sensitization [21] and potentiates conditioned place preference, analgesia and anticonvulsant induced by morphine [34]
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