Abstract:
Nicotine dependence and withdrawal leads to psychosomatic symptoms characterized by anxiety, depression-like behavior, hyperalgesia that contribute to relapse. Sulfonamides have been reported to modulate GABA and antagonize NMDA receptors, and NMDA receptor antagonists reverse nicotine sensitization. Keeping in view the diverse neuropharmacological profile of sulphonamides, effects of 4-fluoro-N-(4sulfamoylbenzyl) benzene sulfonamide (4-FBS) in acquisition and expression of nicotine withdrawal-induced abstinence signs, depression in locomotion, and hyperalgesia was quantified. Ultimately, the animals were killed, and the amounts of dopamine, noradrenaline, adenosine, and its metabolites were measured in key brain areas using HPLC-UV. For induction of dependence nicotine was administered at a dose of 2 mg/kg i.p. for 14 days in 4 divided doses. 4-FBS was given at a dose of 20, 40, and 60 mg/kg.4-FBS at 40 and 60 mg/kg has significantly reduced abstinence score in acute studies after 48 and 72 h of withdrawal, while in sub-acute studies 4-FBS at all three doses reduced abstinence score after 24, 48 and 72 h of nicotine. 4-FBS at 40 and 60 mg/kg significantly increased locomotor activity in comparison to nicotine withdrawal after 48, and 72 h while in sub-acute studies it significantly increased locomotor activity at the same doses. 4-FBS, found to have antinociceptive effects in both thermal and mechanical hyperalgesia at 24, 48, and 72 h of nicotine withdrawal. Nicotine withdrawal-induced depression-like behavior was reversed by 4-FBS at 40 and 60 mg/kg after 72 h of withdrawal. 4-FBS at various doses showed an anti-addictive profile by normalizing dopamine, adenosine, and noradrenaline levels both in the striatum and hippocampal brain regions. As well as upsurge of adenosine, inosine, and hypoxanthine levels were also normalized in the striatum and hippocampus implying its neuroprotective effect. The behavioral, and neurochemical finding concluded, a significant effect of 4-FBS on acquisition and expression of nicotine dependence and withdrawal.
Page(s):
64-64
DOI:
DOI not available
Published:
Journal: Abstract Book on International Conference on Life Sciences (ICLS-23) 11-12 May 22-23, Volume: 0, Issue: 0, Year: 2023
Keywords:
Depression
,
Nicotine
,
Dopamine
,
dependence
,
Withdrawal
,
Adenosine